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INTRODUCTION

● (See "Overview of infertility" .)

● (See "Female infertility: Causes" .)

● (See "Female infertility: Treatments" .)

● (See "Causes of male infertility" .)

Female infertility

On this page, when to see a doctor, risk factors.

Infertility is defined as trying to get pregnant with frequent, unprotected sex for at least a year with no success.

Infertility results from female factors about one-third of the time and both female and male factors about one-third of the time. The cause is either unknown or a combination of male and female factors in the remaining cases.

Female infertility causes can be difficult to diagnose. There are many treatments, depending on the infertility cause. Many infertile couples will go on to conceive a child without treatment.

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• A Book: Mayo Clinic Family Health Book, 5th Edition
• A Book: Mayo Clinic Guide to Fertility and Conception

The main symptom of infertility is the inability to get pregnant. A menstrual cycle that's too long (35 days or more), too short (less than 21 days), irregular or absent can mean that you're not ovulating. There might be no other signs or symptoms.

When to seek help can depend on your age:

• Up to age 35, most doctors recommend trying to get pregnant for at least a year before testing or treatment.
• If you're between 35 and 40, discuss your concerns with your doctor after six months of trying.
• If you're older than 40, your doctor might suggest testing or treatment right away.

Your doctor might also want to begin testing or treatment right away if you or your partner has known fertility problems, or if you have a history of irregular or painful periods, pelvic inflammatory disease, repeated miscarriages, cancer treatment, or endometriosis.

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For pregnancy to occur, every step of the human reproduction process has to happen correctly. The steps in this process are:

• One of the two ovaries releases a mature egg.
• The egg is picked up by the fallopian tube.
• Sperm swim up the cervix, through the uterus and into the fallopian tube to reach the egg for fertilization.
• The fertilized egg travels down the fallopian tube to the uterus.
• The fertilized egg attaches (implants) to the inside of the uterus and grows.

Female reproductive system

The ovaries, fallopian tubes, uterus, cervix and vagina, also called the vaginal canal, make up the female reproductive system.

Fertilization and implantation

During fertilization, the sperm and egg unite in one of the fallopian tubes to form a zygote. Then the zygote travels down the fallopian tube, where it becomes a morula. Once it reaches the uterus, the morula becomes a blastocyst. The blastocyst then burrows into the uterine lining a process called implantation.

In women, a number of factors can disrupt this process at any step. Female infertility is caused by one or more of the factors below.

Ovulation disorders

Ovulating infrequently or not at all accounts for most cases of infertility. Problems with the regulation of reproductive hormones by the hypothalamus or the pituitary gland or problems in the ovary can cause ovulation disorders.

• Polycystic ovary syndrome (PCOS). polycystic ovary syndrome (PCOS) causes a hormone imbalance, which affects ovulation. PCOS is associated with insulin resistance and obesity, abnormal hair growth on the face or body, and acne. It's the most common cause of female infertility.
• Hypothalamic dysfunction. Two hormones produced by the pituitary gland are responsible for stimulating ovulation each month — follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Excess physical or emotional stress, a very high or very low body weight, or a recent substantial weight gain or loss can disrupt production of these hormones and affect ovulation. Irregular or absent periods are the most common signs.
• Primary ovarian insufficiency. Also called premature ovarian failure, this is usually caused by an autoimmune response or by premature loss of eggs from your ovary, possibly as a result of genetics or chemotherapy. The ovary no longer produces eggs, and it lowers estrogen production in women under age 40.
• Too much prolactin. The pituitary gland can cause excess production of prolactin (hyperprolactinemia), which reduces estrogen production and can cause infertility. This can also be caused by medications you're taking for another condition.

Damage to fallopian tubes (tubal infertility)

Damaged or blocked fallopian tubes keep sperm from getting to the egg or block the passage of the fertilized egg into the uterus. Causes of fallopian tube damage or blockage can include:

• Pelvic inflammatory disease, an infection of the uterus and fallopian tubes due to chlamydia, gonorrhea or other sexually transmitted infections
• Previous surgery in the abdomen or pelvis, including surgery for ectopic pregnancy, in which a fertilized egg implants and develops somewhere other than the uterus, usually in a fallopian tube

Endometriosis

Endometriosis occurs when tissue that typically grows in the uterus implants and grows in other places. This extra tissue growth — and the surgical removal of it — can cause scarring, which can block fallopian tubes and keep an egg and sperm from uniting.

Endometriosis can also disrupt implantation of the fertilized egg. The condition also seems to affect fertility in less-direct ways, such as damage to the sperm or egg.

Uterine or cervical causes

Several uterine or cervical causes can interfere with the egg implanting or increase the risk of miscarriage:

• Benign polyps or tumors (fibroids or myomas) are common in the uterus. Some can block fallopian tubes or interfere with implantation, affecting fertility. However, many women who have fibroids or polyps do become pregnant.
• Problems with the uterus present from birth, such as an unusually shaped uterus, can cause problems becoming or remaining pregnant.
• Cervical stenosis, a narrowing of the cervix, can be caused by an inherited malformation or damage to the cervix.
• Sometimes the cervix can't produce the best type of mucus to allow the sperm to travel through the cervix into the uterus.

Unexplained infertility

In some cases, the cause of infertility is never found. A combination of several minor factors in both partners could cause unexplained fertility problems. Although it's frustrating to get no specific answer, this problem can correct itself with time. But you shouldn't delay treatment for infertility.

More Information

• Fallopian tubes: Is pregnancy possible with only one?
• Hypothyroidism and infertility: Any connection?

Certain factors may put you at higher risk of infertility, including:

• Age. The quality and quantity of a woman's eggs begin to decline with age. In the mid-30s, the rate of follicle loss speeds, resulting in fewer and poorer quality eggs. This makes conception more difficult, and increases the risk of miscarriage.
• Smoking. Besides damaging your cervix and fallopian tubes, smoking increases your risk of miscarriage and ectopic pregnancy. It's also thought to age your ovaries and deplete your eggs prematurely. Stop smoking before beginning fertility treatment.
• Weight. Being overweight or significantly underweight may affect ovulation. Getting to a healthy body mass index (BMI) might increase the frequency of ovulation and likelihood of pregnancy.
• Sexual history. Sexually transmitted infections such as chlamydia and gonorrhea can damage the fallopian tubes. Having unprotected sex with multiple partners increases your risk of a sexually transmitted infection that may cause fertility problems later.
• Alcohol. Excess alcohol consumption can reduce fertility.

For women thinking about getting pregnant soon or in the future, these tips might help:

• Maintain a healthy weight. Overweight and underweight women are at increased risk of ovulation disorders. If you need to lose weight, exercise moderately. Strenuous, intense exercise of more than five hours a week has been associated with decreased ovulation.
• Quit smoking. Tobacco has multiple negative effects on fertility, as well as your general health and the health of a fetus. If you smoke and are considering pregnancy, quit now.
• Avoid alcohol. Heavy alcohol use may lead to decreased fertility. And any alcohol use can affect the health of a developing fetus. If you're planning to become pregnant, avoid alcohol, and don't drink alcohol while pregnant.
• Reduce stress. Some studies have shown that stress can cause couples to have poorer results with infertility treatment. Try to reduce stress in your life before trying to become pregnant.

Aug 27, 2021

• Frequently asked questions: Treating infertility FAQ 137. American College of Obstetricians and Gynecologists. https://www.acog.org/womens-health/faqs/treating-infertility. Accessed April 17, 2021.
• Kuohung W, et al. Causes of female infertility. https://www.uptodate.com/contents/search. Accessed April 14, 2021.
• What is infertility? Centers for Disease Control and Prevention. https://www.cdc.gov/reproductivehealth/features/what-is-infertility/index.html. Accessed April 14, 2021.
• Infertility. Office on Women's Health. https://www.womenshealth.gov/a-z-topics/infertility. Accessed April 14, 2021.
• Frequently asked questions: Evaluating infertility FAQ 136. American College of Obstetricians and Gynecologists. https://www.acog.org/womens-health/faqs/evaluating-infertility. Accessed April 14, 2021.
• Cena H, et al. Obesity, polycystic ovary syndrome, and infertility: A new avenue for GLP-1 receptor agonists. Journal of Clinical Endocrinology and Metabolism. 2020; doi:10.1210/clinem/dgaa285.
• Kuohung W, et al. Evaluation of female infertility. https://www.uptodate.com/contents/search. Accessed April 14, 2021.
• Kuohung W, et al. Treatments for female infertility. https://www.uptodate.com/contents/search. Accessed April 14, 2021.
• Female infertility. AskMayoExpert. Mayo Clinic; 2020.
• Timmons D, et al. Ovarian hyperstimulation syndrome: A review for emergency clinicians. American Journal of Emergency Medicine.2019; doi:10.1016/j.ajem.2019.05.018.
• Rizzuto I, et al. Risk of ovarian cancer for women treated with ovarian stimulating drugs for infertility (Review). Cochrane Database of Systematic Reviews. 2019; doi: 10.1002/14651858.CD008215.pub3.
• Diseases & Conditions
• Female infertility symptoms & causes
• Tipped uterus

Associated Procedures

• In vitro fertilization (IVF)

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Clinical Reproductive Medicine and Surgery pp 281–301 Cite as

Female Infertility

• Elizabeth J. Klein 3 ,
• Roxanne Vrees 3 &
• Gary N. Frishman 3  
• First Online: 18 June 2022

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Infertility is a common medical condition that affects up to 15% of couples. In addition to the wide range of potential etiologies, infertility is complex in ways unique within obstetrics and gynecology, given its involvement of both the patient and her partner as well as the variable insurance coverage and access to resources. The diagnosis of infertility, alongside the evaluation and treatment, can be an emotionally challenging and uniquely difficult time for patients and their partners alike, often impacting their quality of life and relationship. Importantly, with the delays in child-bearing in our society, the impact of a woman’s age and the biological clock are playing a critical role. Fortunately, with advances in diagnostic and therapeutic maneuvers including assisted reproductive technologies, there are many options that can maximize a woman’s chances for building a family. This chapter outlines the initial evaluation of a patient with in fertility including the most common etiologies, the diagnostic work-up, and current and evolving treatment options.

• Ovarian reserve
• Selective estrogen receptor modulator
• Uterosacral ligament
• Antral follicle count
• Acanthosis nigricans

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Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiology. Clin Biochem. 2018;62:2–10. https://doi.org/10.1016/j.clinbiochem.2018.03.012 .

Article   PubMed   Google Scholar  

Gelbaya TA, Potdar N, Jeve YB, Nardo LG. Definition and epidemiology of unexplained infertility. Obstet Gynecol Surv. 2014;69(2):109–15. https://doi.org/10.1097/OGX.0000000000000043 .

Marshburn PB. Counseling and diagnostic evaluation for the infertile couple. Obstet Gynecol Clin North Am. 2015;42(1):1–14. https://doi.org/10.1016/j.ogc.2014.10.001 .

National public health action plan for the detection, prevention, and management of infertility. p. 26.

Google Scholar  

American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2015;103(6):e44–50. https://doi.org/10.1016/j.fertnstert.2015.03.019 .

Article   Google Scholar  

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 194: Polycystic ovary syndrome. Obstet Gynecol. 2018;131(6):e157–71. https://doi.org/10.1097/AOG.0000000000002656 .

Azziz R, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456–88. https://doi.org/10.1016/j.fertnstert.2008.06.035 .

Walker MH, Tobler KJ. Female infertility. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020. Accessed: 04 Jan 2021. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK556033/ .

Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017;96(6):659–67. https://doi.org/10.1111/aogs.13082 .

Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010;116(1):223–36. https://doi.org/10.1097/AOG.0b013e3181e8b073 .

McGovern PG. Is vitamin D important for in vitro fertilization success? Fertil Steril. 2020;114(5):962. https://doi.org/10.1016/j.fertnstert.2020.08.009 .

Chu J, Gallos I, Tobias A, Tan B, Eapen A, Coomarasamy A. Vitamin D and assisted reproductive treatment outcome: a systematic review and meta-analysis. Hum Reprod. 2018;33(1):65–80. https://doi.org/10.1093/humrep/dex326 .

Iliuta F, Pijoan JI, Lainz L, Exposito A, Matorras R. Women’s vitamin D levels and IVF results: a systematic review of the literature and meta-analysis, considering three categories of vitamin status (replete, insufficient and deficient). Hum Fertil. 2020:1–19. https://doi.org/10.1080/14647273.2020.1807618 .

Rao M, Zeng Z, Zhao S, Tang L. Effect of levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism and thyroid autoimmuneity undergoing in vitro fertilization/intracytoplasmic sperm injection: an updated meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2018;16(1):92. https://doi.org/10.1186/s12958-018-0410-6 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

ten Broek RPG, et al. Burden of adhesions in abdominal and pelvic surgery: systematic review and met-analysis. BMJ. 2013;347:f5588. https://doi.org/10.1136/bmj.f5588 .

Article   PubMed   PubMed Central   Google Scholar  

American College of Obstetricians and Gynecologists. Carrier screening. https://www.acog.org/en/womens-health/faqs/carrier-screening .

Frishman GN, Spurrell TP, Heber WW. Folic acid. Preconception knowledge and use by infertile women. J Reprod Med. 2001;46(12):1025–30.

CAS   PubMed   Google Scholar  

Kaye AD, et al. Herbal medicines: current trends in anesthesiology practice--a hospital survey. J Clin Anesth. 2000;12(6):468–71. https://doi.org/10.1016/s0952-8180(00)00195-1 .

Article   CAS   PubMed   Google Scholar  

Kumar S, Sharma A, Kshetrimayum C. Environmental & occupational exposure & female reproductive dysfunction. Indian J Med Res. 2019;150(6):532–45. https://doi.org/10.4103/ijmr.IJMR_1652_17 .

Williams M, Hill CJ, Scudamore I, Dunphy B, Cooke ID, Barratt CL. Sperm numbers and distribution within the human fallopian tube around ovulation. Hum Reprod. 1993;8(12):2019–26. https://doi.org/10.1093/oxfordjournals.humrep.a137975 .

Gould JE, Overstreet JW, Hanson FW. Assessment of human sperm function after recovery from the female reproductive tract. Biol Reprod. 1984;31(5):888–94. https://doi.org/10.1095/biolreprod31.5.888 .

Wu HY, et al. Lesbian, gay, bisexual, transgender content on reproductive endocrinology and infertility clinic websites. Fertil Steril. 2017;108(1):183–91. https://doi.org/10.1016/j.fertnstert.2017.05.011 .

Kyweluk MA, Reinecke J, Chen D. Fertility preservation legislation in the United States: potential implications for transgender individuals. LGBT Health. 2019;6(7):331–4. https://doi.org/10.1089/lgbt.2019.0017 .

Banna M. Craniopharyngioma: based on 160 cases. Br J Radiol. 1976;49(579):206–23. https://doi.org/10.1259/0007-1285-49-579-206 .

Sklar CA. Craniopharyngioma: endocrine abnormalities at presentation. Pediatr Neurosurg. 1994;21(Suppl. 1):18–20. https://doi.org/10.1159/000120856 .

Schlechte J, et al. Prolactin-secreting pituitary tumors in amenorrheic women: a comprehensive study*. Endocr Rev. 1980;1(3):295–308. https://doi.org/10.1210/edrv-1-3-295 .

Vallette-Kasic S, et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab. 2002;87(2):581–8. https://doi.org/10.1210/jcem.87.2.8272 .

Smith G, Roberts R, Hall C, Nuki G. Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs. Br J Rheumatol. 1996;35(5):458–62. https://doi.org/10.1093/rheumatology/35.5.458 .

Zanagnolo V, Dharmarajan AM, Endo K, Wallach EE. Effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, prostaglandin, and progesterone production in the rabbit. Fertil Steril. 1996;65(5):1036–43. https://doi.org/10.1016/s0015-0282(16)58283-1 .

Freda PU, Wardlaw SL, Post KD. Unusual causes of sellar/parasellar masses in a large transsphenoidal surgical series. J Clin Endocrinol Metab. 1996;81(10):3455–9. https://doi.org/10.1210/jcem.81.10.8855784 .

Infertility workup for the women’s health specialist: ACOG committee opinion, number 781. Obstet Gynecol. 2019;133(6):e377–84. https://doi.org/10.1097/AOG.0000000000003271 .

Barekat M, Ahmadi S. Hypertensive disorders in pregnant women receiving fertility treatments. Int J Fertil Steril. 2018;12(2):92–8. https://doi.org/10.22074/ijfs.2018.5232 .

Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015;29(4):498–506. https://doi.org/10.1016/j.bpobgyn.2014.10.014 .

Miller JW, Crapo L. The medical treatment of cushing’s syndrome. Endocr Rev. 1993;14(4):443–58. https://doi.org/10.1210/edrv-14-4-443 .

American Society for Reproductive Medicine. ASRM Patient Education Booklet: Hirsutism and Polycystic Ovarian Syndrome.

Gupta M, Saini V, Poddar A, Kumari S, Maitra A. Acquired Clitoromegaly: a gynaecological problem or an obstetric complication? J Clin Diagn Res JCDR. 2016;10(12):QD10–1. https://doi.org/10.7860/JCDR/2016/23212.9072 .

Long WN. Pelvic examination. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations. 3rd ed. Boston: Butterworths; 1990. Accessed: Apr. 09, 2021. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK286/ .

Practice Committee of American Society for Reproductive Medicine. Vaccination guidelines for female infertility patients: a committee opinion. Fertil Steril. 2013;99(2):337–9. https://doi.org/10.1016/j.fertnstert.2012.08.027 .

Thyroid Function Tests. American Thyroid Association. https://www.thyroid.org/thyroid-function-tests/ . Accessed 09 Apr 2021.

Spencer C, et al. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem. 1987;33(8):1391–6.

Article   CAS   Google Scholar  

Wathen NC, Perry L, Lilford RJ, Chard T. Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range. Br Med J (Clin Res Ed). 1984;288(6410):7–9.

Martinez AR, Bernardus RE, Vermeiden JPW, Schoemaker J. Time schedules of intrauterine insemination after urinary luteinizing hormone surge detection and pregnancy results. Gynecol Endocrinol. 1994;8(1):1–5. https://doi.org/10.3109/09513599409028450 .

Scott RT, Hofmann GE. Prognostic assessment of ovarian reserve. Fertil Steril. 1995;63(1):1–11.

Hansen LM, Batzer FR, Gutmann JN, Corson SL, Kelly MP, Gocial B. Evaluating ovarian reserve: follicle stimulating hormone and oestradiol variability during cycle days 2–5. Hum Reprod. 1996;11(3):486–9. https://doi.org/10.1093/humrep/11.3.486 .

Muttukrishna S, McGarrigle H, Wakim R, Khadum I, Ranieri DM, Serhal P. Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology? BJOG. 2005;112(10):1384–90. https://doi.org/10.1111/j.1471-0528.2005.00670.x .

Ebner T, Sommergruber M, Moser M, Shebl O, Schreier-Lechner E, Tews G. Basal level of anti-Müllerian hormone is associated with oocyte quality in stimulated cycles. Hum Reprod. 2006;21(8):2022–6. https://doi.org/10.1093/humrep/del127 .

Hendriks DJ, Mol B-WJ, Bancsi LFJMM, Te Velde ER, Broekmans FJM. Antral follicle count in the prediction of poor ovarian response and pregnancy after in vitro fertilization: a meta-analysis and comparison with basal follicle-stimulating hormone level. Fertil Steril. 2005;83(2):291–301. https://doi.org/10.1016/j.fertnstert.2004.10.011 .

Navot D, Rosenwaks Z, Margalioth EJ. Prognostic assessment of female fecundity. Lancet Lond Engl. 1987;2(8560):645–7. https://doi.org/10.1016/s0140-6736(87)92439-1 .

Roach MK, Andreotti RF. The normal female pelvis. Clin Obstet Gynecol. 2017;60(1):3–10. https://doi.org/10.1097/GRF.0000000000000259 .

Falcone T, Hurd WW, editors. Clinical reproductive medicine and surgery: a practical guide. 2nd ed. New York: Springer-Verlag; 2013. https://doi.org/10.1007/978-1-4614-6837-0 .

Book   Google Scholar  

Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninckx PR, Olive D. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev. 2010;1:CD001398. https://doi.org/10.1002/14651858.CD001398.pub2 .

Reindollar RH, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010;94(3):888–99. https://doi.org/10.1016/j.fertnstert.2009.04.022 .

Legro R. S. et al. , Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. https://doi.org/10.1056/NEJMoa1313517 , 2014. https://www.nejm.org/doi/10.1056/NEJMoa1313517 . Accessed 09 Apr 2021.

Penzias A, et al. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril. 2020;113(2):305–22. https://doi.org/10.1016/j.fertnstert.2019.10.014 .

Diamond MP, et al. Letrozole, gonadotropin, or clomiphene for unexplained infertility. N Engl J Med. 2015;373(13):1230–40. https://doi.org/10.1056/NEJMoa1414827 .

Intrauterine Insemination. https://www.asrm.org/topics/topics-index/intrauterine-insemination/ . Accessed 09 Apr 2021.

What is Assisted Reproductive Technology? | Reproductive Health | CDC. Nov. 09, 2020. https://www.cdc.gov/art/whatis.html . Accessed 09 Apr 2021.

IVF Blastocyst Pictures & Blastocyst Stage Embryo Grading Photos. https://advancedfertility.com/fertility-gallery/blastocyst-images/ . Accessed 09 Apr 2021.

Society for Assisted Reproductive Technology. Success rates. https://www.sart.org/patients/a-patients-guide-to-assisted-reproductive-technology/general-information/success-rates/ . Accessed 08 Apr 2021.

Society for Assisted Reproductive Technology. What are my chances with ART? https://www.sartcorsonline.com/Predictor/Patient . Accessed 08 Apr 2021.

Psychological Evaluation. https://www.asrm.org/resources/coding/coding-qa/coding-corner/psychological-evaluation/ . Accessed 09 Apr 2021.

Galhardo A, Moura-Ramos M, Cunha M, Pinto-Gouveia J. The infertility trap: how defeat and entrapment affect depressive symptoms. Hum Reprod. 2016;31(2):419–26. https://doi.org/10.1093/humrep/dev311 .

Arpin V, Brassard A, El Amiri S, Péloquin K. Testing a new group intervention for couples seeking fertility treatment: acceptability and proof of concept. J Sex Marital Ther. 2019;45(4):303–16. https://doi.org/10.1080/0092623X.2018.1526836 .

Chin H, Howards P, Kramer M, Mertens A, Spencer J. Racial disparities in seeking Care for Help Getting Pregnant. Paediatr Perinat Epidemiol. 2015;29(5):416–25. https://doi.org/10.1111/ppe.12210 .

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Klein, E.J., Vrees, R., Frishman, G.N. (2022). Female Infertility. In: Falcone, T., Hurd, W.W. (eds) Clinical Reproductive Medicine and Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-99596-6_12

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The Genetics of Infertility: Current Status of the Field

Infertility is a relatively common health condition, affecting nearly 7% of all couples. Clinically, it is a highly heterogeneous pathology with a complex etiology that includes environmental and genetic factors. It has been estimated that nearly 50% of infertility cases are due to genetic defects. Hundreds of studies with animal knockout models convincingly showed infertility to be caused by gene defects, single or multiple. However, despite enormous efforts, progress in translating basic research findings into clinical studies has been challenging. The genetic causes remain unexplained for the vast majority of male or female infertility patients. A particular difficulty is the huge number of candidate genes to be studied; there are more than 2,300 genes expressed in the testis alone, and hundreds of those genes influence reproductive function in humans and could contribute to male infertility. At present, there are only a handful of genes or genetic defects that have been shown to cause, or to be strongly associated with, primary infertility. Yet, with completion of the human genome and progress in personalized medicine, the situation is rapidly changing. Indeed, there are 10-15 new gene tests, on average, being added to the clinical genetic testing list annually.

Introduction

Infertility is a highly complex disorder of the reproductive system. There are 2 forms of male or female sterility: Primary and secondary. The primary form affects germ cell structure or physiology, causing arrest of germ cell development and ultimately cell death. Primary female infertility includes premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, and leiomyoma. Primary male sterility disrupts spermatogenesis and is associated with abnormal semen (i.e., abnormal sperm count, morphology, or motility), but often the semen is normal (idiopathic infertility).

Secondary infertility arises due to systemic or syndromic genetic defects, including developmental, endocrine, and metabolic defects. Genetic syndromes that manifest male or female infertility are fragile X syndrome, Kartagener's syndrome, myotonic dystrophy, Noonan syndrome, Fanconi anemia, sickle cell anemia, β-thalassemia, etc. Other notable conditions include disorders of sex development ( DAX1, CBX2, SRY , SOX9 , RSPO1 ) [ 1 - 6 ], reproductive dysgenesis disorders ( AMH, AMHR2, ARX, DHH, NR5A1, WNT4, WT1 )[ 6 ], hypogonadotrophic hypogonadism and Kallmann syndrome ( KAL1, FGFR1, PROKR2, GNRH1, TAC3, LEP, NSMF, CHD7, DAX1, KISS1 )[ 7 ], ambiguous genitalia and androgen insensitivity ( AR ) [ 8 ], and congenital bilateral absence of vas deferens ( CFTR ); ( Tables 1 & 2 ) [ 9 , 10 ].

Genes, Chromosome Aberrations, Genomic CNVs and Disorders of Male Infertility.

Incidence and OMIM numbers are shown when available for respective disorders. Ch. Location – chromosome location, del(,) – deletion

Genes, Chromosome Aberrations, Genomic CNVs and Disorders of Female Infertility

Incidence and OMIM are shown when available for respective disorders. Ch. Location – chromosome location, t(,) – translocation, del(,) – deletion, COL – collagen, Ch region – chromosome region

Endocrine defects comprise disruption of steroid synthesis and metabolism, and are caused by CYP17 , CYP21 , and CYP21A2 mutations [ 6 , 11 , 12 ]. Also, various metabolic defects (e.g., galactosemia)[ 13 ] and mutations in mitochondrial energy pathways ( POLG1 and mitochondrial DNA genes) cause toxic effects and lead to secondary female or male infertility[ 14 ]. All genetic defects can be divided into the following categories: chromosome aberrations, DNA copy number variants (micro deletions and duplications), single-gene disorders, complex conditions and epigenetic disorders.

Chromosomal defects in male infertility

Constitutional chromosome aberrations are the most frequent cause of male infertility, detected in up to 20% of infertile men with semen defects; i.e., azoospermia, and oligozoospermia [ 6 , 11 , 12 , 15 ]. The aberrations include numerical defects, such as the XYY karyotype in Klinefelter syndrome or its variants and structural rearrangements, Robertsonian translocations, balanced reciprocal translocations, and inversions. Rarely, infertile men with normal karyotype have chromosome aberrations in sperm [ 16 ]. Increased germ cell defects have been reported for chromosomes 21, 22, X, and Y [ 15 , 16 ].

Klinefelter syndrome

(KS, karyotype 47,XXY) is the most common chromosomal aberration, detected in up to 14% of infertile patients with azoospermia [ 17 ]. Klinefelter patients manifest language delay and learning and behavioral problems [ 18 ]. Their testis histology show germ cell degeneration, while serum levels of hormones are abnormal, with a decline in testosterone level and elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [ 12 , 17 , 18 ]. The 47,XXY karyotype accounts for nearly 90% of the patients, while other variants are rare [ 17 ]. Usually, the extra X is result of chromosome nondisjunction in male or female meiosis [ 18 ]. Nearly 10% of KS patients are mosaic 47,XXY/46,XY. Although the sperm of Klinefelter men usually have a normal 23,X or 23,Y haploid genome, an increased rate of autosomal and sex chromosome aneuploidies was reported in KS men's offspring [ 19 ].

47,XYY syndrome

This syndrome occurs in 1:1000 men, but is more common among infertile males [ 15 , 17 ]. Infertile men with the 47,XYY karyotype are otherwise healthy. While semen analyses of 47,XYY males frequently indicate oligozoospermia or azoospermia, the majority of them are fertile, with normal semen parameters [ 16 ]. It has been shown that germ cells with an extra Y chromosome from men with the 47,XYY karyotype have abnormal meiotic pairing, suggesting disrupted meiosis, eventual sperm apoptosis, and subsequent oligozoospermia and infertility [ 15 , 16 ].

Structural chromosomal abnormalities

(SCAs) include deletions, duplications, translocations (balanced, imbalanced, and Robertsonian), and inversions. Overall, SCAs occur in nearly 5% in infertile men (0.5% in the general population) [ 11 , 12 , 17 ]. Most frequently, SCAs are found in patients with azoospermia and oligozoospermia. Interestingly, while autosomal defects (3%) are more common in oligozoospermia, structural aberrations involving sex chromosomes are associated with azoospermia (12.6%) [ 20 , 21 ]. There are two alternative models that explain the aberration effect: 1) It blocks spermatogenesis via abnormal chromosome synapsis in crossover and meiosis arrest, 2) the aberration disrupts a dosage-sensitive gene, resulting in spermatogenesis arrest and infertility [ 15 , 16 , 20 , 21 ].

Y chromosome microdeletions

There are 3 frequent microdeletions of the azoospermia factor (AZF) region. The AZF deletions are detected in up to 15% of azoospermic and about 5% of oligozoospermic patients [ 17 , 22 , 23 ]. The deletions affect three distinct regions AZFa, AZFb, and AZFc. The AZFa is nearly 0.8 Mb region that maps to proximal region Yq11.21. AZFb and AZFc map to regions Yq11.22 and Yq11.23, respectively. The AZF deletions influence, overall, 27 unique genes or gene families [ 24 , 25 ].

AZFa deletions are uncommon and associated with Sertoli cell–only syndrome; testicular histology shows complete germ cell loss and degeneration of seminiferous tubules [ 15 , 17 ]. The AZFa deletion is a result of nonallelic homologous recombination (NAHR) between two nearly identical DNA repeats. The general view is that the deletion of 2 genes, USP9Y and DBY ( DDX3Y ) cause the pathology.

AZFb deletions cause spermatogenesis arrest at the spermatocyte stage, loss of mature sperm and milder azoospermia [ 17 , 22 , 24 ]. The AZFb region has a complex genomic structure and high-identity repeats (palindromic amplicons) that spread in opposite directions up to AZFc [ 25 ]. This structure is prone to NAHR between AZFb and AZFc, resulting in 2 frequent deletions, 6.2 Mb and 7.7 Mb [ 24 , 25 ]. The 6.2 Mb AZFb deletions remove multiple copies of testis-specific CDY , HSFY , RBMY , and PRY genes. The 7.7 Mb deletion spans an extra 1.5 Mb in the AZFc region (AZFb+c deletion).

AZFc deletions are found in around 12% of infertile azoospermic men and about 6% with severe oligozoospermia [ 24 , 25 ]. The AZFc 3.5 Mb region contains multiple copies of 5 large repeats - b1, b2, b3, b4, and gr - that are placed in opposite directions and predispose to various partial deletions [ 25 ]. Loss of 4 dosage-sensitive, germ-specific gene families - BPY2 , PRY2 , DAZ, and CDY1 - is associated with full AZFc deletions [ 22 , 23 , 25 ]. A common view is that a low dosage of DAZ (Deleted in Azoospermia) causes oligozoospermia. The DAZ1-4 genes encode germ cell–specific RNA-binding proteins, and their loss affects translation in germ cells and leads to meiosis arrest [ 25 ]. Among smaller AZFc deletions, only gr/gr deletions are associated with increased risk of semen defects. The majority of AZFc deletions occur de novo , while partial gr/gr deletions can be passed from father to son [ 17 , 25 ]. It was shown that inherited gr/gr deletion increases risk of a complete AZFc deletion in the offspring [ 11 , 12 ].

Robertsonian translocations

are the most common SCAs in humans, resulting in a derivative chromosome composed of 2 long arms from 2 acrocentric chromosomes (13, 14, 15, 21, and 22). Commonly, RT carriers are healthy but have a high risk of infertility, aberrations in offspring, and spontaneous abortions. The aberrations are found in nearly 1.6% of infertile male patients. The most frequent RTs are der(13;14) and der(14;21), with incidences of 1:1,000 and 1:5,000, respectively [ 12 , 15 , 16 , 26 , 27 ]. Nearly 20% of male carriers of der(13;14) are infertile [ 27 ]. Most mature spermatozoa with RT are normal or balanced (75–90%) as a result of alternate segregation. However, these translocations are associated with disrupted pairing in crossingover, lead to trivalent formation and subsequent meiotic arrest, and result in oligozoospermia or azoospermia [ 26 , 27 ]. Male carriers of RTs involving chromosome 21 are more likely to have the disomic gametes likely to produce embryos with trisomy 21. However, male RT carriers are often subfertile, lessening that likelihood [ 15 ].

Balanced translocations

predispose to the formation of a quadrivalent structure between aberrant chromosomes and their normal homologues in meiotic germ cells. This leads to a high proportion (up to 80%) of unbalanced spermatozoa [ 20 , 21 ]. Carriers of balanced aberrations are otherwise healthy but often present with infertility [ 15 , 20 , 21 ]. This infertility is due to fertilization by an abnormal gamete with an unbalanced SCA, leading to an unbalanced embryo unlikely to survive. Thus, preimplantation genetic diagnosis benefits carriers of balanced SCAs by identifying embryos with normal or balanced chromosomes. Although carriers with chromosome inversions are generally are healthy, often present with recurrent pregnancy loss and offspring with abnormal chromosomes [ 15 , 20 , 21 ]. Since inverted segments pair and form an inversion loop in meiosis, its position and inversion size determine the outcome of meiotic pairing. In general, large pericentric inversions (spanning over half of chromosome) are likely to produce unbalanced SCAs and are frequently observed in infertile men [ 16 , 21 ].

Testicular disorder of sex development (DSD)

The DSD, known as 46,XX male syndrome, is a rare pathology seen in nearly 1/25,000 newborn males [ 12 , 17 ]. Most of DSD patients have an X;Y translocation with Y-linked gene SRY (sex region Y chromosome) is placed on one of the X chromosomes [ 1 , 28 ]. 46,XX males with SRY and testicular DSD have normal male genitalia, but show spermatogenesis arrest and develop severe testicular atrophy and azoospermia [ 29 ]. The SRY encodes the critical testis-determining transcription factor that activates a number of downstream transcription factors involved in testes formation. SOX9 is a direct target of SRY, and its overexpression can mimic male development without SRY . Mutations and small duplications of the SOX9 upstream regulatory region were demonstrated in SRY -negative XX [ 3 , 29 ] males. Alternatively, increased expression of SOX9 can be induced by steroidogenic factor 1, NR5A1 and SOX3 [ 29 ]. Recently, R-spondin 1 ( RSPO1 ) mutations were shown to cause an XX male condition [ 2 ].

Complex structural chromosome aberrations

(CSAs) involve at least 3 regions in an exchange. Balanced SCAs are rare in individuals with a history of recurrent abortions and infertility. Molecular studies of SCA breakpoints indicate that the complexity and number of breaks cannot predict fertility status. Risk of spontaneous abortion for CSA carriers is estimated at around 50%. Intracytoplasmic sperm injection is not recommended for male SCA carriers due to the low amount of balanced sperm produced [ 21 , 30 ].

Genomic copy number variants (CNVs)

are submicroscopic aberrations of 0.05 to 3 Mb that cannot be detected by regular chromosome testing. To date, 2 microarray technologies used to detect loss or gain CNVs: single nucleotide polymorphism (SNP) array and the comparative genomic hybridization (CGH) array that detects specific probes in comparison to a control specimen. Recent whole-genome and X chromosome CGH studies detected multiple CNVs, with loss and gain that probably affect critical dosage-sensitive genes on sex or autosomal chromosomes [ 31 - 33 ]. These studies note that infertile men usually do not have an increased number of CNVs, suggesting that their infertility is likely due to specific defects in single or multiple gene(s). Other studies, using genome-wide SNP arrays, revealed multiple CNVs and regions of homozygosity that could worsen the effect of multiple recessive mutations present in the human genome [ 34 - 36 ]. A recent study of CNVs via SNP array demonstrated various individual CNVs in multiple male germ cell–specific genes [ 34 ]. Of interest are multiple loss-of-function deletions of the DMRT1 in patients with various types of azoospermia (e.g., Sertoli cell–only syndrome, testicular failure, or maturation arrest). These genomic aberrations range from 0.132 to 2 Mb, deleting a few exons or the entire gene. The gene encodes an ortholog of an avian sex determination factor and was implicated in nonsyndromic gonadal dysgenesis [ 34 ]. Two recent studies showed that 200 Kb deletions on 12q14 chromosome remove testis-specific DPY19L2 . The deletions are a major cause of globozoospermia (abnormally round sperm head morphology) and detected in nearly 67% of patients [ 37 , 38 ]. The gene encodes a C. elegans ortholog involved in initial stages of round spermatid polarization [ 38 ].

Single-gene disorders

The study of male infertility caused by single-gene mutations is a rapidly changing field. In the past decade, we have seen a number of reports newly demonstrating the association of various genes with male infertility. Here we present a list of noteworthy single-gene disorders, while a larger list of single-gene mutations with initial reports is shown in Table 1 . The best known single-gene disorder is congenital bilateral aplasia of the vas deferens (CBAVD) with obstructive azoospermia. Mutations in cystic fibrosis transmembrane conductance regulator ( CFTR ) were reported in more than 90% of CBVAD patients [ 10 , 39 ]. The gene encodes the ATP-binding chloride channel and regulates chloride secretion and sodium ion absorption [ 40 ]. A general view is that a pair of the CFTR mutations, IVS8-5T in intron 8 and another gene coding mutation, causes isolated CBAVD. However, if the patient has two coding CFTR mutations in both alleles, he will develop classical cystic fibrosis syndrome, including multiple-organ clinical symptoms and male infertility [ 10 ].

AR (androgen receptor) encodes testis-specific testosterone receptor. The gene has been associated with androgen insensitivity (AIS) disorder that ranges from females with testes (complete AIS) to normal and otherwise healthy infertile males (partial AIS) [ 8 ]. To date, more than 300 gene mutations have been reported, with multiple forms of testosterone insensitivity and abnormal development of internal and external genitalia. Recently, two studies using conventional and Cre/Lox conditional Ar -null male mice recreated human disorders [ 41 , 42 ]. They showed female external sex development and testis atrophy with spermatocyte-stage arrest, resembling AIS human pathology.

AURKC (aurora kinase C) is highly expressed in testis and encodes a protein that is probably involved in cytokinesis during germ cell mitosis and meiosis [ 43 , 44 ]. Mutations in the gene were reported in a number of infertile males with entirely abnormal sperm morphology and sperm polyploidy [ 45 ] The initial report identified a founder loss-of-function mutation; however, subsequent studies have expanded the list of gene mutations, supporting the importance of AURKC for sperm morphology [ 46 ].

HSF2 encodes a testis-expressed heat-shock transcription factor 2. Recent study of Hsf2 -null male mice demonstrated embryonic lethality, neuronal defects, and a reduced spermatogenesis that includes meiotic disruption and increased sperm apoptosis with seminiferous tubule dysgenesis [ 47 , 48 ]. A subsequent study of HSF2 in 766 azoospermic males revealed missense mutations in approximately 1% of patients, suggesting high heterogeneity of the azoospermia [ 49 ].

KLHL10 (kelch-like 10) is exclusively expressed in elongating and elongated spermatids. The gene encodes a sperm-specific substrate-targeting module of Cullin 3 ubiquitin ligase and regulates protein ubiquitination and sperm maturation [ 50 ]. Null Klhl10 in male mice causes haploinsufficiency with meiotic arrest, absence of mature spermatozoa in semen and male infertility [ 50 ]. A study of human oligozoospermia identified missense and splicing mutations in KLHL10 in nearly 2% of patients that were not observed in controls [ 51 ]. Further functional analysis reported damaging effect of missense mutations. Some gene mutations showed variable effect, ranging from severe to mild oligozoospermia.

NR5A1 encodes steroidogenic factor 1 (SF1), crucial in male and female gonadal development and steroidogenesis. Nr5a1 -null male mice present with adrenal agenesis, female internal genitalia, and gonadal absence [ 52 ]. Initial human studies of the gene reported mutations association with female sex development and infertility in males. However, 2 recent studies of male infertility found different NR5A1 missense mutations associated with 1–4 % of men with oligozoospermia [ 53 , 54 ].

PRM1 encodes the testis-specific nuclear protein protamine 1 that replaces histones in postmeiotic sperm. Null PRM1 mutations in male mice showed a haploinsufficiency effect and had a chromatin compaction defect, sperm DNA damage, and severe teratozoospermia [ 55 ]. A study of PRM1 in men with similar semen defects identified missense mutations in 10% of infertile patients [ 56 , 57 ]. However, later studies were used insufficient patient and/or control populations and led to conflicting results [ 57 - 59 ]. Recently, mutation search was expanded to PRM2 , PRM3 , and TNP2 located adjacent to the protamine gene cluster, reporting novel mutations [ 60 ].

SLC26A8 encodes a sperm-specific sulfate exchange channel (also known as testis anion transporter, TAT1 ) that regulates CFTR and is vital for sperm motility [ 61 ]. Male mice with null SLC26A8 show sperm with abnormal head, no motility, and male sterility [ 62 ]. Recently, 2 studies revealed that nearly 2–5% of patients with asthenozoospermia (reduced sperm motility) have various gene mutations with deleterious effects [ 63 , 64 ].

SOHLH1 (spermatogenesis- and oogenesis-specific basic helix-loop-helix 1) encodes a critical testis-specific transcription factor for essential for spermatogonial differentiation [ 65 ]. Male mice with homozygous deletion of Sohlh1 demonstrated spermatocyte arrest, testicular failure, and azoospermia [ 65 ]. A subsequent study of the gene in male patients with testicular failure and nonobstructive azoospermia (NOA) supported this notion [ 66 ]. Two missense and one splicing mutation in the SOHLH1 were detected in about 3% of patients with NOA. Further in vitro functional assay provided evidence that the mutations had a damaging effect [ 66 ].

SPATA16 (spermatogenesis-associated protein 16) encodes a testis-specific Golgi apparatus protein with tetratricopeptide motif. The original study of one consanguineous family with male infertility and globozoospermia (abnormally round-headed sperm) reported homozygous mutations in the autosomal gene, SPATA16, in 3 affected brothers [ 67 ]. It was shown that the sperm head defects were due to SPATA16 protein involvement in acrosome formation.

ZPBP1 encodes zona pellucida binding protein 1. The protein is located in the acrosomal extracellular matrix of mature sperm and is involved in the initial steps of oocyte fertilization. Zpbp1 -null male mice show acrosome fragmentation and abnormal sperm head morphology resembling globozoospermia [ 68 ]. A study of human ZPBP1 revealed that nearly 4% of patients with abnormal sperm-head morphology have missense and splicing gene mutations [ 69 ].

Epigenetic and posttranscriptional modifications

Epigenetic abnormalities were recently reported in male infertility. One study tested genome-wide methylation defects in 27,000 CpG dinucleotides in sperm from men with abnormal sperm chromatin packaging and patients displaying defective spermatogenesis [ 70 ]. It described altered DNA methylation patterns in 3 out of 43 patients, suggesting that a systemic methylation defect contributes to male infertility. A second study identified novel posttranscriptional UBE2B mRNA mutations in approximately 4% of patients with severe oligozoospermia [ 71 ]. This report is consistent with results of earlier study of Ube2b -null male mice with spermatogenic meiotic disruption, increased apoptosis, and male sterility and suggests that such modifications substantially contribute to an abnormal protein load and sperm disruption and [ 72 ].

Female infertility

Reproductive defects and genital tract developmental defects are not uncommon in women, yet little is known about the genetics behind them. During sexual development, congenital malformations of the reproductive tract may occur that affect fertility; these include anatomical abnormalities of the Mullerian ducts, uterus, endometrium, Fallopian tubes, and ovaries [ 6 ]. Premature menopause in women of reproductive age and the increasing prevalence of intentionally delayed pregnancy, in Western countries at least, also contribute to female infertility [ 73 ].

Chromosomal aberrations

syndrome, also known as trisomy X , is one of most common causes of premature ovarian insufficiency (POI); it occurs in 1 in 1,000 female births. While the majority of women with trisomy X present as normal, some suffer from POI or from malformations of the genitourinary tract [ 74 ]. The aberration happens due to chromosome nondisjunction errors in meiosis I or II in oogenesis.

Turner syndrome

also known as monosomy X or 45,XO, chromosome disorder in females, has an incidence of 1:2,000 births. The loss of chromosome X in the oocyte is a result of chromosome nondisjunction in meiosis. 45,XO females display skeletal abnormalities, congenital heart defects, and physical attributes such as short stature, a webbed neck, low hairline, flat chest, and gonadal dysgenesis with signs of amenorrhea or ovarian failure. Females mosaic for Turner syndrome present with a milder form, often noted due to infertility. 45,X/47,XXX is not a common mosaic presentation, but does present similarly to 45,X/46,XX, with ovarian function declining quickly and leading to infertility [ 75 ].

Genomic aberrations, copy number variants (CNVs)

Recently, a number of microarray studies reported genomic regions associated with female infertility, including the complex disorders endometriosis and primary ovarian failure (POF). They provided stepping stones toward in-depth whole-genome analysis and the discovery of novel genes that would not have been detected with the use of older technologies. One SNP array study identified 6 novel microdeletions affecting at least one gene, each, from a total of 198 autosomal CNVs (microdeletions and microduplications) in 89 women with POF [ 76 ]. Among deleted genes, two previously described POF genes, SYCE1 and CPEB1 , were found. Null mutations in these two genes were responsible for ovarian failure in female mice [ 77 , 78 ]. Another CGH study tested genomic CNVs in 74 patients with POF and ovarian dysfunction [ 79 ]. Multiple genes, such as PLCB1 , RB1CC1 , MAP4K4 , RBBP8 , IMMP2L , FER1L6 , and MEIG1 , involved in meiosis, DNA repair, or folliculogenesis, were identified as possible candidate genes for POF and ovarian dysfunction. Following CGH studies identified new infertility-associated candidate genes and unveiled new details of the pathophysiology [ 79 , 80 ].

Fragile X syndrome

is a disorder characterized mainly by mental retardation, long faces, large ears, and prominent jaws. The syndrome was first reported in 1969 with constriction of the long arm on the X chromosome [ 81 ]. It has an incidence of 1:5,161[ 82 ]. The critical gene for fragile X is FMR1, fragile X mental retardation gene, located at Xq27.3. The pathology is caused by expansion of the CGG repeat in the gene's 5’ untranslated region to a premutation state of between 56 and 199 repeats (a complete mutation has over 200 repeats). Generally, FMR1 premutations are found in 16% of POF females, with about 2% of the cases being sporadic and 14–21% familial [ 82 , 83 ]. Carrier screening of FMR1 premutation is recommended for women of advanced maternal age or with a family history of fragile X.

Galactosemia

Many women with galactosemia manifest hypergonadotropic hypogonadism, presenting with secondary amenorrhea [ 84 , 85 ]. Premature ovarian failure is independent of age. A candidate gene that has shown to be associated with galactosemia and endometriosis is the GALT gene, although conflicting results in various studies have reduced its likelihood at being causal [ 13 , 84 ]. Early genetic counseling about the related risk of infertility and pediatric endocrinologist assistance greatly improve the prognosis of ovarian failure for girls with galactosemia [ 13 , 86 ]. Since most women with galactosemia are infertile, pregnancy is achieved by oocyte or pre-embryo donation.

Primary ovarian failure (POF)

is defined as either complete or incomplete failure of the ovaries (also known as primary ovarian insufficiency, POI). Recently, several genes have been discovered that show incomplete loss of function of the ovary, leading to the term “primary ovarian insufficiency” (POI). A number of genes have been associated with POF/POI. X-linked genes include FMR1 and bone morphogenetic protein 15 (BMP15) located at the Xp11.2 region [ 87 , 88 ]. Among autosomal gene mutations often found in women with POF/POI are AR, CDKN1B, CYP19A1, GDF9, FIGLA, FOXL2, FOXO1a, FOXO3a, INHA, LHX8, NOBOX, NANOS3, FSHR, and SALL4 .

FOXL2 encodes an ovarian development-specific transcription factor with forkhead box L2. The forkhead box is a DNA-binding domain that plays a key role in the protein function. Dominant mutations in FOXL2 cause premature ovarian failure 3 [ 89 ]. The gene is also responsible for the blepharophimosis, ptosis, and epicanthus syndrome, which may include POF [ 90 ].

GDF9 (growth/differentiation factor 9) and GDF9B ( BMP15 ) are necessary for ovarian folliculogenesis and somatic cell function in both mice and humans. Initial genetic studies in women with POF discovered multiple missense mutations in 3–4% of patients [ 91 ]. Subsequent studies of POF in women of various ethnic backgrounds reported more mutations in these two genes.

FIGLA (factor in germline alpha) is located at 2p13.3 and encodes a germ cell–specific basic helix-loop-helix transcription factor. It regulates the expression of the zona pellucida- and oocyte-specific genes. A knockout of FIGLA in female mice prevents the formation of primordial follicles, and oocyte numbers drop rapidly after birth [ 92 ]. The initial study of FIGLA identified mutations in approximately 4% of POF patients [ 93 ]. Two women had missense mutations and two had other gene deletions that resulted in a frameshift and haploinsufficiency [ 93 ].

NOBOX (newborn ovary homeobox) is located at 7q35 and encodes a transcriptional regulator with a homeobox motif. Study of Nobox -null female mice indicates that this gene is critical for early folliculogenesis [ 94 ], and an independent human study found NOBOX defects in POF patients [ 95 ]. Later, two missense mutations in the homeobox domain were found in 6.2% of patients of Caucasian or African descent [ 96 ].

SALL4 (SAL-like 4) is located at 20q13.2 and encodes putative zinc finger transcription factor and plays a role in the pluripotency of oocytes. In Nobox -deficient mouse ovaries, SALL4 is downregulated, suggesting it is activated by NOBOX [ 94 ]. In a study of 100 Han Chinese women with nonsyndromic POF, two probable gene mutations were discovered in POF subjects and not in the control group [ 97 ]. Remaining known genes associated with POF have been recessive, producing a variety of phenotypes and causing idiopathic infertility ( Table 2 )[ 6 ].

also referred to as fibroids, are benign tumors found in the smooth muscle layers of the uterus. It is not uncommon to have irregular bleeding and pain, sometimes necessitating a hysterectomy. The number of tumors varies among those affected, and can change in conjunction with hormones. During pregnancy, the tumor lesions have a tendency to increase in size. There is a prevalence of lesions among black women, who undergo hysterectomies twice as often as whites [ 98 , 99 ]. Somatic chromosomal rearrangements or deletions are found in the 12q and 7q regions, respectively [ 100 ]. Deletions within 7q are observed in about 20% of leiomyomas [ 100 ]. Whole genome sequencing implicated CUX1 , ZNHIT1 and CUL1 as key genes within 7q deletions [ 101 ]. In addition, a mutations affecting oncogenes, metabolism, and follicle stimulating hormone signaling, and changes in COL4A5 - COL4A6 , HMGA2 and RAD51B were identified [ 101 ]. New studies using conventional and next-generation sequencing techniques identified mutations in the MED12 gene as a major contributor to leiomyoma [ 102 - 104 ]. Nearly 60% of patients with the pathology have MED12 mutations.

Polygenic, complex female infertility

Endometriosis.

is a complex disease, characterized by the inflammation and bleeding of the endometrium. It affects 5-10% of females. Often there is infertility and pain due to endometrial tissue in the pelvic region outside of the uterus [ 98 , 105 ]. Those with affected first degree relatives have five to eight times increased risk for the disease. Genetic association and linkage studies have identified some candidate genes, SNPs, and CNVs but follow-up studies are needed to replicate the studies and narrow down critical regions ( Table 2 ). One study determined a significant linkage to 10q26, but the linkage peak was too broad to identify a single gene as a causative factor of endometriosis [ 106 ]. Among two genome-wide association (GWAS) studies conducted in Australia and Japan in 2011 and 2010 [ 107 , 108 ], only one common locus was found - in the 1p36 region- which contains WNT4 , a gene responsible for cell proliferation and which plays a key role in embryogenesis [ 109 ]. Prior studies have also noted this region's involvement in endometriosis [ 98 ].

Polycystic ovarian syndrome

(PCOS) is a complex endocrine disorder with heterogeneous genetic causes. It is found in about 7% of women of reproductive age. Aside from metabolic issues that may be associated with PCOS, such as obesity and type 2 diabetes mellitus, common symptoms are irregularities in the menstrual cycle, polycystic ovaries, secondary amenorrhea, anovulation, hirsutism, and reduced fertility due to oversized, dysfunctional follicles [ 99 , 110 - 112 ]. The adrenal-form adult-onset disorder is due primarily to enzyme deficiencies, often causing pseudo-hermaphroditism and hirsutism. Nonadrenal PCOS phenotypes differ in how they manifest and in their pathophysiology. There appears to be dominant inheritance, yet no specific gene(s) has been identified as the cause for PCOS, rendering it idiopathic [ 99 ]. Studies of multiple candidate genes including FBN3, FST , INS, INSR, TCF7L2, CAPN10, FTO, SHBG, PCOS1 , SRD5A1 , SRD5A2 , and CYP11A1 have shown association with PCOS [ 98 , 111 - 122 ]. However, these genes have also been shown significant associations with other disorders such as obesity, diabetes, and insulin resistance, which are commonly associated with PCOS. These results suggest the complex nature of PCOS. To date, a direct correlation with PCOS has been shown for one gene, INSR . The insulin receptor gene has shown the highest likelihood as a susceptibility gene in the Han Chinese after being identified in a GWAS study, which also identified 3 additional PCOS loci (2p16.3, 2p21, 9q33.3) [ 114 ]. Two studies were able to replicate the results for one identified gene of interest, DENND1A , a guanine nucleotide exchange factor [ 114 , 123 ]. As yet, the cause of PCOS is unknown; both, genetic and environmental factors must be taken into consideration. Current treatment and management of the symptoms of PCOS include ovulation induction [ 112 ].

Many men and women affected by infertility or disorders that lead to decreased fertility have turned to assisted reproductive technology (ART). Recent estimates show nearly 5 million newborns have been assisted by ART [ 124 ]. It is known that a woman's fecundity decreases with advancing age. Also, the modern tendency to delay childbirth contributes to the increased use of ART. Yet, there are several concerns about the safety and possible negative outcomes of the ICSI treatment, such as pregnancy complication or termination, risk of various birth defects, and childhood developmental and mental defects [ 124 ]. It is important that all couples undergoing infertility treatment should be informed of the risks, benefits, and possible outcomes through the use of genetic testing and counseling. As more genes are discovered, and the etiology of infertility disorders become better understood, the management and treatment of infertility will improve as well.

Conflict of Interest

M Zorrilla has received research grants and travel reimbursements from the NIH.

AN Yatsenko has received research grants and travel reimbursements from the NIH.

Human and Animal Rights and Informed Consent

This article contains studies with human or animal subjects performed by any of the authors.

Papers of particular interest, published recently, have been highlighted as:

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• Open access
• Published: 04 April 2024

Acceptance and commitment therapy adapted for women with infertility: a pilot study of the Infertility ACTion program

• Ashley A. Balsom 1 ,
• Bridget Klest 1 ,
• Bethany Sander 1 &
• Jennifer L. Gordon 1  

Reproductive Health volume  21 , Article number:  43 ( 2024 ) Cite this article

Metrics details

Approximately one in six couples are currently infertile, defined as unable to achieve pregnancy despite 12 or more months of active attempts to conceive. Experiencing infertility has been disproportionately associated with an array of psychological difficulties, particularly in women. However, currently available psychological interventions have had minimal benefits for distress, anxiety, or depression related to infertility.

A one-arm pilot study was conducted to test the acceptability of a newly created acceptance and commitment therapy-based self-guided program—Infertility ACTion. Twenty women, located in Canada, completed the program and completed measures assessing expectancy of improvement, treatment credibility, participant satisfaction, treatment completion and retention, psychological flexibility, fertility quality of life, depression, and anxiety. Participants were also asked to provide feedback on how the researchers could improve the intervention. Paired sample t-tests were conducted to compare pre- and post-intervention outcomes.

Sixteen out of 20 participants completed the entire intervention. Reported treatment expectancy, credibility and satisfaction were favorable. Eighty-one percent of participants reported that they would recommend the program to a friend and 88% thought the program was worth their time. Medium increases in psychological flexibility and fertility quality of life were observed. Improvements in anxious and depressive symptoms were in the small to medium range but were not significant. Participants had several recommendations for program improvement.

Conclusions

This acceptance and commitment therapy-based self-guided program proved to be an acceptable treatment for infertility-related distress. Participant feedback will be used to adjust the current intervention in preparation for a more rigorous randomized-controlled trial testing this program.

Peer Review reports

Introduction

Infertility, defined as an impairment of a person’s capacity to reproduce as an individual or with a partner, affects approximately 13% of the population [ 1 , 2 ]. In cisgendered heterosexual couples, women Footnote 1 have been found to experience more of the psychological burden, perhaps because the onus to seek information and undergo fertility testing and treatment tends to be on the intended pregnant partner [ 3 , 4 ]. In fact, half of infertile women describe infertility as the most upsetting event of their life whereas only 15% of their male partners do [ 5 ]. One-third of women undergoing medically assisted reproduction meet criteria for an anxiety disorder or major depressive disorder [ 6 , 7 ]. Attempting to conceive without medical intervention is associated with similar rates of psychopathology [ 8 , 9 ]. While the psychological burden of infertility is well documented, currently available psychological interventions have proven largely ineffective. The most recent meta-analysis of psychological interventions for infertility identified 58 randomized controlled trials and found that such interventions have only small effects on infertility-related distress [ 10 ]. Efficacy did not differ according to intervention type or format. These findings highlight a need for efficacious mental health interventions for this population.

Acceptance and Commitment Therapy (ACT) is considered part of the ‘third-wave’ of cognitive behaviour therapies. While rooted in traditional cognitive behavioural approaches, ACT incorporates a focus on other skills, particularly mindfulness, more than traditional approaches. The goal of ACT is to encourage psychological flexibility by exploring one’s relationship with one’s thoughts, feelings, memories, and physical sensations. Psychological flexibility is defined as the ability to be in contact with private experiences (i.e., thoughts and feelings) in the present moment while behaving in a way that is consistent with one’s values [ 11 ]. In other words, psychological flexibility reflects an individual’s ability to live life to the fullest despite mental health symptoms like low mood or anxiety. Though ACT has modest support as a treatment for obsessive–compulsive disorder, depression, anxiety, and psychosis, according to the American Psychological Association (APA) division 12, it has strong support for treating mental health problems associated with chronic or persistent pain [ 12 ]. ACT for chronic pain largely aims to encourage individuals to focus less on their pain and to focus more on engaging in activities that are meaningful to them despite their pain. Such an approach may translate well to infertility-related distress; infertility has been associated with a narrowed focus on trying to get pregnant and a decreased involvement in previously-enjoyed activities [ 8 , 13 ], similar to chronic pain. For example, a woman experiencing infertility may avoid spending time with her friend who is pregnant, or stop working out because of fears that exercise may negatively impact fertility.

To date, there have been only three studies from the Middle East testing the use of ACT for individuals experiencing infertility, with promising results [ 14 , 15 , 16 ]. The interventions ranged from 8 to 20 sessions and were delivered via individual and group therapy formats [ 14 , 15 , 16 ]. In North America, there has been one case study reporting success in using ACT in helping a distressed couple experiencing infertility [ 17 ]. However, there have not been any self-administered ACT interventions for infertility. Self-administered mental health interventions have numerous advantages over traditional in-person formats, including increased accessibility and decreased cost. Furthermore, recent meta-analytic evidence suggests that self-help mindfulness-based interventions are beneficial for depression, anxiety, stress, and quality of life in public health settings [ 18 ]. Our team therefore aimed to develop and pilot a brief ACT-based self-help mental health intervention for women experiencing distress related to infertility.

The current study served as a one-arm feasibility study. Treatment feasibility was assessed via a number of indicators, including expectancy of improvement, treatment credibility, participant satisfaction, participant completion and retention, and changes in psychological flexibility, fertility quality of life, depression, and anxiety. Participants were also asked to provide feedback on how the researchers could improve the intervention.

Intervention development

Six modules were created—one to cover each of the six core processes in ACT: acceptance, cognitive defusion, present moment focus, self as context, values, and committed action. A script was drafted for each module by AAB and reviewed and edited by BK, JLG, and two female patient advisors who have lived experience with infertility. These scripts were then turned into a video by pairing a PowerPoint presentation with voiceover. In order to maximize participant adherence, especially considering that many participants would be undergoing burdensome fertility treatments, the research team aimed to keep each of the modules under 15 min long, with homework to be completed between modules. In creating the modules, several ACT-based manuals were consulted [ 19 , 20 ]. The content was adapted to infertility using the research team’s knowledge of the psychology of infertility, the patient advisors’ input, and consulting the case study by Peterson and Eifert [ 15 ] for inspiration. The finished product was reviewed and approved by the team’s patient advisors. A brief description of each of the modules is provided in Table  1 .

The Infertility ACTion Program was designed to be a self-help intervention paired with scripted emails from the research team. Participants received a module each week via email on a day chosen by them. Two days after the module was sent, they were sent a second email reminding them to watch the module video and assigning homework for that week. Finally, an online survey was sent at the end of each week, requesting that participants report the total number of minutes spent engaging in the assigned homework.

Participants

Participants were recruited through online infertility support groups throughout Canada. Individuals were deemed eligible if they had been attempting to conceive for 12 or more months or were currently undergoing medically assisted reproduction and were the intended gestational carrier. Eligible participants had to endorse at least a moderate amount of distress, which was defined as a score below 52 on the Fertility Quality of Life scale [ 21 ]. Participants were ineligible if they scored seven or above on the Suicide Behaviours Questionnaire–Revised, a score range that has been found to have a sensitivity of 0.93 and a specificity of 0.95 in the identification of suicide risk in adult populations [ 22 ]. Participant recruitment began on June 22nd, 2022, and finished July 25th, 2022.

Individuals found to be eligible completed a Zoom-facilitated enrollment session confirming participants’ eligibility for the study, providing information about the project, and obtaining informed consent. Participants completed the pre-intervention, weekly, and post-intervention measures.

Pre-intervention measures

Demographic and reproductive health history questionnaire.

Participants were asked to report demographic information and to complete questions about their reproductive health.

Patient Health Questionnaire-9 (PHQ-9; [ 23 ])

The PHQ-9 is a 9-item questionnaire based on DSM-IV criteria for depressive disorders. Items on the PHQ-9 are on a 4-point Likert scale ranging from 0 ( Not at all ) to 3 ( Nearly every day ). The internal consistency for the current study was Cronbach’s alpha (α) = 0.74.

Generalized Anxiety Disorder-7 (GAD-7; [ 24 ])

The GAD-7 is a 7-item questionnaire based on DSM-IV criteria for generalized anxiety disorder. Items on the GAD-7 are on a 4-point Likert scale ranging from 0 ( Not at all ) to 3 ( Nearly every day ). The current study demonstrated good internal consistency (Cronbach’s alpha (α) = 0.86).

Fertility Quality of Life Questionnaire (FertiQoL; [ 25 ])

The FertiQoL is a 36-item questionnaire. The questionnaire focuses on three areas of quality of life: core quality of life, treatment-related quality of life and life and physical health quality of life. Items are on a 5-point Likert scale ranging from 0 ( Completely, Very Dissatisfied, Always, An Extreme Amount ) to 4 ( Not at all, Very Satisfied, Never, Not at All ). The Core FertiQoL had an internal consistency of Cronbach’s alpha α = 0.78 with the subscales ranging from Cronbach’s alpha α’s = 0.60-0.86.

Revised Dyadic Adjustment Scale (RDAS [ 26 ])

The RDAS is a 14-item measure of the quality and adjustment of a couple’s relationship. The RDAS provides three subscales, including the Dyadic Consensus Subscale, Dyadic Satisfaction Subscale, and Dyadic Cohesion Subscale. It has been found to have good construct validity with both distressed and non-distressed couples [ 27 ]. In the current sample, internal consistency was α = 0.88.

Multidimensional Psychological Flexibility Inventory (MPFI [ 28 ])

The MPFI is a 60-item measure of psychological flexibility. The MPFI examines 12 dimensions of flexibility and inflexibility inspired by the hexaflex model of ACT. The MPFI explores psychological flexibility (acceptance, present moment awareness, self as context, defusion, values, committed action) and inflexibility (experiential avoidance, lack of contact with the present moment, self as content, fusion, lack of contact with values, and inaction). The internal consistency of the MPFI was α = 0.84 for flexibility and α = 0.83 for inflexibility.

The Credibility/Expectancy Questionnaire (CEQ [ 29 ])

It is a 6-item measurement of credibility and expectancy with items ranging from 1–9 or 0–100%. The CEQ has been found to have good interrater consistency and test–retest reliability [ 29 ].

All measures were scored consistent with published recommendations for scoring (e.g., FertiQoL Scoring https://sites.cardiff.ac.uk/fertiqol/scoring/ ). They were scored using syntax in SPSS version 28.0.

Weekly measures

Each week, participants rated their depressive via the PHQ-9, anxious symptoms via the GAD-7, and infertility-related quality of life via the FertiQoL. Participants also rated how helpful they found that week’s module and that week’s homework assignment in helping them cope with their infertility struggles on a scale from 0 to 10 and also reported the number of minutes spent engaged in homework over the past week. An open-ended question also asked to provide feedback about the content of the module, including aspects they found helpful or suggestions for improvement.

Post-intervention measures

The post-intervention measures consisted of the previously administered pre-intervention measures (i.e., PHQ-9, GAD-7, FertiQoL, RDAS, MPFI) in addition to the Treatment Satisfaction Questionnaire, Adverse Effects Questionnaire and open-ended questions about the overall program and suggestions for improvement.

Treatment Satisfaction Questionnaire (TSQ [ 30 ])

The TSQ was used to assess the satisfaction after completing the six-week intervention. The TSQ uses three separate scales, whether they felt that the intervention was worth their time ( yes/no ), feelings of self-efficacy (1 ( greatly reduced ) to 5 ( greatly increased )), and satisfaction with the treatment (1 ( very dissatisfied ) to 5 ( very satisfied )).

Adverse Effects Questionnaire (AEQ [ 31 ])

The measure uses a yes/no scale and contains four items and two follow up questions if adverse effects are endorsed. The AEQ is employed to determine whether participants suffered from any adverse effects during the intervention.

As the current study is a pilot of the Infertility ACTion program, we were primarily interested in the feasibility of the implemented intervention rather than to determine its overall effectiveness. This aimed to investigate the practicality, viability, and potential challenges associated with the intervention. Therefore, we were most interested in participants’ ratings of utility and suggestions for improving the content and modules. That being said, we also examined their descriptive statistics of the pre- and post-intervention measures looking at means and standard deviations. Pre- and post-intervention comparisons were completed using paired samples t-tests. All data was analyzed using SPSS version 28.0.

Participant characteristics

A total of 38 individuals completed the eligibility survey and 28 were found to be eligible as 10 individuals scored too high on the FertiQoL to participate. Of the 28 eligible individuals, 20 agreed to participate. Baseline characteristics of the 20 individuals who agreed to participate are summarized in Table  2 . All participants included in our study were from Canada, half from the Province of Ontario. All participants reported identifying as women. Most of the sample identified as being of European origins and being in a committed relationship. Participants' ages ranged from 26 to 41, with an average in the mid-thirties. Participants were of fairly high socioeconomic status, with 70% having a total annual household income > $113,000. The sample of this study was also highly educated: 45% reported their highest level of completed education as a bachelor’s degree, 20% achieved a master's degree, and 10% completed a doctorate. On average, participants experienced a moderate severity of depressive symptoms, with fifty percent of participants scored above the cut-off score of 10, indicating they experienced clinically significant symptoms of depression (Table  2 ).

Intervention adherence and acceptability

Twenty participants began the Infertility ACTion Program, and 16 completed the entire program and follow-up questionnaire; one participant dropped out after the first week of the intervention, two participants dropped out after the second week, and one participant dropped out after the third week.

Participant responses to the pre-intervention Credibility and Expectancy Questionnaire are reported in Table  3 . Most participants endorsed the program as logical and predicted a 50% improvement in symptoms as a result of participating in the program.

As shown in Table  4 , participants assigned an average helpfulness score of 7.0/10 for the weekly modules and average of 6.6/10 for the weekly homework assignments. They completed an average of 39.6 min of homework each week.

Post-intervention responses to the Treatment Satisfaction Questionnaire are reported in Table  5 . Eleven out of 16 participants were “satisfied” or “very satisfied” with the intervention, 14/16 felt it was worth their time and 13/16 would recommend it to a friend and felt that the intervention increased their confidence in managing their symptoms. On the Adverse Effect Questionnaire, no participants endorsed any adverse effects associated with participating in the program, but 4/16 reported experiencing an unwanted event during the intervention. One participant noted that they felt that this unwanted event impacted their ability to engage with the intervention (Table  5 ).

ACT-based psychological processes

Pre-to-post changes on the Multidimensional Psychological Flexibility Inventory are shown in Table  6 . Effect sizes associated with changes in psychological flexibility and inflexibility – the two main processes by which ACT is hypothesized to benefit emotional wellbeing – both fell within the medium to large range. Among the dimensions of “flexibility”, changes in “acceptance” were found to be the largest; among the dimensions of “inflexibility”, changes in the “self as context” subscale was largest.

Mental health outcomes

Table 7 depicts the pre-to-post intervention changes in mental health outcomes. Though changes in depressive and anxious symptoms were in the small to medium range, changes in fertility quality of life fell in the medium range. Of the subscales of the FertiQoL, the “emotional” subscale was associated with the largest effect.

Intervention feedback

Qualitative feedback suggests that participants valued the analogies and examples used throughout the program and that the program was specifically tailored to infertility. They also appreciated the convenient format of the program and that the weekly videos were short and that each module ended with a wrap-up summary. Several participants appreciated the mindfulness exercises included in the program.

At the same time, participants recommended several potential changes to the program. Some feedback was contradictory, such as when some participants reported disliking an exercise and the same number of participants report specifically benefiting from that exercise. Similarly, participants liked that the videos were so short but also wanted more examples included and further discussion of numerous topics. Participants feedback can be found in the Additional file 1 .

This study pilot tested a self-directed ACT-based intervention adapted for infertility, created by our team, in collaboration with women experiencing infertility. Of the 20 women who enrolled in the pilot, 16 finished all six weeks of the intervention and the follow-up survey, translating to a 20% dropout rate, which is favourable when compared to a recent meta-analysis of online-based trials for depression finding a mean dropout rate across studies of 50% [ 32 ]. Research testing self-administered versions of both ACT and CBT for mental health problems unrelated to infertility have observed similarly high dropout rates [ 33 , 34 ].

ACT which focuses on acceptance, mindfulness, and living a values life, without fighting against what is lost [ 20 ], has been shown to improve anxiety, depression, and distress in individuals with advanced cancer, families facing challenging health circumstances, and individuals experiencing chronic disease [ 35 , 36 , 37 ]. It is unsurprising that this approach aligns with some of the challenges faced by women dealing with infertility, as it encourages individuals to accept difficult emotions and thoughts while pursuing a meaningful life.

Prior to starting the intervention, participants rated it as highly credible and expected to benefit from the program. Though one might expect a self-directed intervention to have lower credibility or expectancy scores than other modalities [ 38 ], scores observed were similar to those seen for in-person ACT-based and CBT-based interventions [ 39 , 40 ]. Post-intervention satisfaction was also quite high with nearly 90% reporting that they would recommend the program to a friend.

ACT-based interventions have been explored in a self-directed format in various contexts, demonstrating its potential acceptance across therapeutic formats [ 41 ]. This suggests that ACT can be delivered effectively though online platforms, making it accessible for self-directed use. This has also been tested in exploring self-directed formats with specific populations like individuals with type 2 diabetes, advanced cancer, and individuals with acquired brain injury [ 35 , 42 , 43 ]. The Infertility ACTion program may be the next targeting intervention for a health population to create accessible and affordable access to evidence based psychological interventions.

Some of the recommended changes from participants would be easy to implement, such as providing more mindfulness exercises and allowing participants to use their own mindfulness recordings. The program could also be made longer (e.g., to eight weeks) to include some of the recommended content. An alternative approach would be to create short supplementary modules on some of the topics identified, such as jealousy and anger.

Future iterations of this program may include changes aimed at improving homework compliance as the average number of minutes spent on homework each week ranged from 38- 45, equating to an average of under seven minutes each day. Other studies have reported homework compliance of closer to 30–45 min a day [ 44 ]. Since homework compliance has been found to predict positive psychological outcomes in self-administered and online interventions [ 45 , 46 , 47 ], it seems worthwhile attempting to increase the time spent completing homework. One simple tactic, which was recommended by several participants, is to increase the number of reminders to complete the homework. Certain homework assignments may also benefit from some editing; for example, a few participants recommended replacing the “80th birthday” exercise to the “65th birthday” exercise to avoid triggering an existential crisis. Such adjustments may increase homework helpfulness ratings, which was found to be 6.6/10 in the current study. In turn, greater homework completion and satisfaction may increase the effects of the program on mental health.

Though small changes to the Infertility ACTion Program may be warranted, program completion was associated with medium to large changes in both flexibility and inflexibility, the processes by which ACT is believed to benefit well-being. Of the flexibility subscales, acceptance and cognitive defusion exhibited the largest changes; of the inflexibility subscales, lack of contact with the present moment and self as context exhibited the largest changes. In terms of mental health outcomes, a medium effect was observed for overall fertility quality of life, with the emotional subscale showing the largest increase. In contrast, declines in depressive and anxious symptoms were small. This finding is consistent with the fact that while ACT is an intervention recognized by APA Division 12 for use with chronic pain, it is not currently recognized as having strong evidence for use with depression or anxiety [ 48 ]. Indeed, the focus of ACT is not on symptom reduction but rather on symptom acceptance and the commitment to live one’s life to the fullest despite one’s symptoms. Thus, it is perhaps not surprising that improvements in flexibility are accompanied by an improvement in quality of life despite only small changes in symptoms of psychopathology.

The findings of this study should be considered in light of a few limitations. First, the sample size was small and better educated than the population average, perhaps limiting the generalizability of our findings. Second, module and homework completion were assessed via self-report and are therefore subject to inaccuracies. Third, only short-term mental health outcomes were assessed; it is possible that mental health may have continued to improve as participants continued to implement the skills they learned throughout the program. Finally, the current study consisted of a one-arm within-person study, which makes it difficult to differentiate the effects of the intervention from the effects of the passage of time. A randomized controlled trial will be better suited to addressing this issue in the future.

Infertility currently affects one in six women and is becoming increasingly prevalent as more women choose to delay childbearing. For many, it will be the most upsetting experience of their lives. Currently, adapted interventions for infertility-related distress have had limited success in clinically significant reductions in symptomology for women with infertility. ACT is an evidence-based intervention that has received limited exploration for women with infertility. This pilot has demonstrated that an ACT-based self-directed intervention is feasible with this population; more rigorous research and the above-mentioned changes are needed to help clarify the efficacy of this intervention.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available to protect the identities of the participants involved. Anonymized data supporting the findings of this study are available from the corresponding author, upon reasonable request.

Throughout this manuscript women will be used to refer to individuals attempting to conceive and possessing a uterus. It is important to consider that not all individuals matching this description will identify as women and may have unique experiences of distress.

American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013;99:63–63.

Article   Google Scholar  

Mascarenhas MN, Cheung H, Mathers CD, Stevens GA. Measuring infertility in populations: constructing a standard definition for use with demographic and reproductive health surveys. Popul Health Metr. 2012;10:1–1.

El Kissi Y, Romdhane AB, Hidar S, Bannour S, Ayoubi Idrissi K, Khairi H, et al. General psychopathology, anxiety, depression and self-esteem in couples undergoing infertility treatment: a comparative study between men and women. Eur J Obstet Gynecol Reprod Biol. 2013;167:185–9.

Article   PubMed   Google Scholar  

Bunting L, Tsibulsky I, Boivin J. Fertility knowledge and beliefs about fertility treatment: findings from the International fertility decision-making study. Hum Reprod. 2013;28:385–97.

Freeman EW, Boxer AS, Rickels K, Tureck R, Mastroianni LJ. Psychological evaluation and support in a program of in vitro fertilization and embryo transfer. Fertil Steril. 1985;43:48–53.

Article   CAS   PubMed   Google Scholar  

Chen T-H, Chang SP, Tsai CF, Juang KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod. 2004;19:2313–8.

Volgsten H, Skoog SA, Ekselius L, Lundkvist Ö, Sundström PI. Prevalence of psychiatric disorders in infertile women and men undergoing in vitro fertilization treatment. Hum Reprod. 2008;23:2056–63.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Balsom AA, Gordon JL. The relationship between psychological coping and mood across the menstrual cycle among distressed women struggling to conceive. J Psychosom Res. 2021;145:e110465–e110465.

Chernoff A, Balsom AA, Gordon JL. Psychological coping strategies associated with improved mental health in the context of infertility. Arch Womens Ment Health. 2020. https://doi.org/10.1007/s00737-020-01029-9 .

Dube L, Bright K, Hayden KA, Gordon JL. Efficacy of psychological interventions for mental health and pregnancy rates among individuals with infertility: a systematic review and meta-analysis. Hum Reprod Update. 2022. https://doi.org/10.1093/humupd/dmac034 .

Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J. Acceptance and commitment therapy: model, processes and outcomes. Behav Res Ther. 2006;44:1–25.

APA Division 12. Psychological treatments. https://div12.org/treatments/ . Accessed 28 Jan 2022.

Cunha M, Galhardo A, Pinto-Gouveia J. Experiential avoidance, self-compassion, self-judgment and coping styles in infertility. Sex Reprod Healthc. 2016;10:41–7.

Hosseinpanahi M, Mirghafourvand M, Farshbaf-Khalili A, Esmaeilpour K, Rezaei M, Malakouti J. The effect of counseling based on acceptance and commitment therapy on mental health and quality of life among infertile couples: a randomized controlled trial. J Educ Health Promot. 2020;9:251.

Article   PubMed   PubMed Central   Google Scholar  

Peterson BD, Eifert GH. Using acceptance and commitment therapy to treat infertility stress. Cogn Behav Pract. 2011;18(4):577–87.

Rahimi E, Attarha M, Majidi A. Effect of acceptance and commitment therapy on the quality of life in infertile women during treatment: a randomized control trial. Int J Womens Health Reprod Sci. 2019;7:483–9.

Peterson B, Eifert G. Treating infertility stress in patients undergoing in vitro fertilization (IVF) using acceptance and commitment therapy (ACT). Fertil Steril. 2009;91:S18–S18.

Taylor H, Strauss C, Cavanagh K. Can a little bit of mindfulness do you good? A systematic review and meta-analyses of unguided mindfulness-based self-help interventions. Clin Psychol Rev. 2021;89: 102078.

Harris R. ACT made simple: an easy-to-read primer on acceptance and commitment therapy. Oakland: New Harbinger Publications; 2019.

Google Scholar  

Hayes SC. Get out of your mind and into your life: The new acceptance and commitment therapy. Oakland: New Harbinger Publications; 2005.

Koert E, Takefman J, Boivin J. Fertility quality of life tool: update on research and practice considerations. Hum Fertil. 2021;24:236–48.

Article   CAS   Google Scholar  

Osman A, Bagge CL, Gutierrez PM, Konick LC, Kopper BA, Barrios FX. The suicidal behaviors questionnaire-revised (SBQ-R): validation with clinical and nonclinical samples. Assessment. 2001;8:443–54.

Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validty of a brief depression severity measure. J Gen Intern Med. 2001;16:606–13.

Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092–7.

Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQoL) tool: development and general psychometric properties. Hum Reprod. 2011;26:2084–91.

Russell Crane D, Middleton KC, Bean RA. Establishing criterion scores for the kansas marital satisfaction scale and the revised dyadic adjustment scale. Am J Fam Ther. 2000;28:53–60.

Busby DM, Christensen C, Crane DR, Larson JH. A revision of the dyadic adjustment scale for use with distressed and nondistressed couples: construct hierarchy and multidimensional scales. J Marital Fam Ther. 1995;21:289–308.

Rolffs JL, Rogge RD, Wilson KG. Disentangling components of flexibility via the hexaflex model: development and validation of the multidimensional psychological flexibility inventory (MPFI). Assessment. 2018;25:458–82.

Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther Exp Psychiatry. 2000;31:73–86.

Dear BF, Titov N, Schwencke G, Andrews G, Johnston L, Craske MG, et al. An open trial of a brief transdiagnostic internet treatment for anxiety and depression. Behav Res Ther. 2011;49:830–7.

Rozental A, Kottorp A, Forsström D, Månsson K, Boettcher J, Andersson G, et al. The Negative Effects Questionnaire: psychometric properties of an instrument for assessing negative effects in psychological treatments. Behav Cogn Psychother. 2019;47:559–72.

Torous J, Lipschitz J, Ng M, Firth J. Dropout rates in clinical trials of smartphone apps for depressive symptoms: a systematic review and meta-analysis. J Affect Disord. 2020;263:413–9.

Carvalho SA, Skvarc D, Barbosa R, Tavares T, Santos D, Trindade IA. A pilot randomized controlled trial of online acceptance and commitment therapy versus compassion-focused therapy for chronic illness. Clin Psychol Psychother. 2022;29:524–41.

Barrett K, Stewart I. A preliminary comparison of the efficacy of online acceptance and commitment therapy (ACT) and cognitive behavioural therapy (CBT) stress management interventions for social and healthcare workers. Health Soc Care Commun. 2021;29:113–26.

Rauwenhoff J, Bol Y, van Heugten C, Batink T, Geusgens C, van den Hout AJHC, et al. Acceptance and commitment therapy for people with acquired brain injury: rationale and description of the BrainACT treatment. Clin Rehabil. 2023. https://doi.org/10.1177/02692155231154124 .

Davis E, Deane FP, Lyons G. An acceptance and commitment therapy self-help intervention for carers of patients in palliative care: protocol of a feasibility randomised controlled trial. J Health Psychol. 2016. https://doi.org/10.1177/1359105316679724 .

Zarei F, Asadpour E, Mohsenzadeh F. The efficacy of acceptance and commitment based therapy on marital satisfaction and self-efficiency of mothers with children with cerebral palsy. J Psychol Sci. 2021. https://doi.org/10.52547/JPS.20.105.1493 .

Bernstein EE, Weingarden H, Greenberg JL, Williams J, Hoeppner SS, Snorrason I, et al. Credibility and expectancy of smartphone-based cognitive behavioral therapy among adults with body dysmorphic disorder. J Obses Compuls Relat Disord. 2023;36:100781.

Scott W, Guildford BJ, Badenoch J, Driscoll E, Chilcot J, Norton S, et al. Feasibility randomized-controlled trial of online acceptance and commitment therapy for painful peripheral neuropathy in people living with HIV: the OPEN study. Eur J Pain. 2021;25:1493–507.

Smeets RJ, Beelen S, Goossens ME, Schouten EG, Knottnerus JA, Vlaeyen JW. Treatment expectancy and credibility are associated with the outcome of both physical and cognitive-behavioral treatment in chronic low back pain. Clin J Pain. 2008;24:305–15.

Pots WTM, Fledderus M, Meulenbeek PAM, ten Klooster PM, Schreurs KMG, Bohlmeijer ET. Acceptance and commitment therapy as a web-based intervention for depressive symptoms: randomised controlled trial. Br J Psychiatry. 2016. https://doi.org/10.1192/bjp.bp.114.146068 .

Ngan HY, Chong YY, Chien WT. Effects of mindfulness- and acceptance-based interventions on diabetes distress and glycaemic level in people with type 2 diabetes: systematic review and meta-analysis. Diabet Med. 2021. https://doi.org/10.1111/dme.14525 .

Fang P, Tan L, Cui J, Yu L. Effectiveness of acceptance and commitment therapy for people with advanced cancer: a systematic review and meta-analysis of randomized controlled trials. J Adv Nurs. 2022. https://doi.org/10.1111/jan.15543 .

Parsons CE, Crane C, Parsons LJ, Fjorback LO, Kuyken W. Home practice in mindfulness-based cognitive therapy and mindfulness-based stress reduction: a systematic review and meta-analysis of participants’ mindfulness practice and its association with outcomes. Behav Res Ther. 2017;95:29–41.

Cammin-Nowak S, Helbig-Lang S, Lang T, Gloster AT, Fehm L, Gerlach AL, et al. Specificity of homework compliance effects on treatment outcome in CBT: evidence from a controlled trial on panic disorder and agoraphobia. J Clin Psychol. 2013;69:616–29.

Kazantzis N, Whittington C, Zelencich L, Kyrios M, Norton PJ, Hofmann SG. Quantity and quality of homework compliance: a meta-analysis of relations with outcome in cognitive behavior therapy. Behav Ther. 2016;47:755–72.

LeBeau RT, Davies CD, Culver NC, Craske MG. Homework compliance counts in cognitive-behavioral therapy. Cogn Behav Ther. 2013;42:171–9.

APA Division 12. Treatment: Acceptance and commitment therapy for chronic pain. https://div12.org/treatment/acceptance-and-commitment-therapy-for-chronic-pain/ . Accessed 28 Jan 2022.

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Acknowledgements

We particularly want to thank all of those who participated in this study. Their valuable insights and support of this project was essential to those process. This research would not be possible without our two patient-partners whose feedback and guidance helped form the intervention to what it is today. We are also grateful to Andreea Ababei for her help in data collection.

This research was supported by the Saskatchewan Health Research Foundation grant 4577. Dr. Gordon is also supported by a Tier II Canadian Institutes of Health (CIHR) Canada Research Chair and Ashley Balsom is supported by a Social Sciences and Humanities Research Council Doctoral Fellowship.

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Ashley A. Balsom, Bridget Klest, Bethany Sander & Jennifer L. Gordon

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Contributions

Conceptualization: Ashley A. Balsom, Bridget Klest, Jennifer Gordon; Formal analysis: Ashley A. Balsom; Funding acquisition: Jennifer L. Gordon; Methodology: Ashley A. Balsom, Jennifer Gordon; Writing—original draft: Ashley A. Balsom; Writing—review and editing: Bethany Sander, Jennifer L. Gordon, Bridget Klest.

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Correspondence to Jennifer L. Gordon .

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All study materials including consent forms, intervention consent, and email scripts were reviewed and approved by the ethics committee at the University of Regina (REB #2022–026). All participants provided written consent before enrolling in the study.

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Additional file 1:.

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Balsom, A.A., Klest, B., Sander, B. et al. Acceptance and commitment therapy adapted for women with infertility: a pilot study of the Infertility ACTion program. Reprod Health 21 , 43 (2024). https://doi.org/10.1186/s12978-024-01766-5

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Received : 22 May 2023

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DOI : https://doi.org/10.1186/s12978-024-01766-5

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• Infertility
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Female infertility

May 22, 2013

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Female infertility. James N Anasti, M.D. Dept OB/GYN. Definition. Infertility Fecundablity Fecundity. Just the Facts. 55/1000. 1790 Birth rate :. 2001 Birth rate:. 14.7/1000. Fertitlity services 1982: . 12% (6.6 mil). Fertility services 1995:. 15% (9.3 mil).

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Female infertility James N Anasti, M.D. Dept OB/GYN

Definition • Infertility • Fecundablity • Fecundity

Just the Facts 55/1000 1790 Birth rate : 2001 Birth rate: 14.7/1000 Fertitlity services 1982: 12% (6.6 mil) Fertility services 1995: 15% (9.3 mil) Services used: 53% ovulatory drugs, 1.6% ART

What physical attribute is an important factor for infertility?

AGE: the Hutterites • Peaks at age 20-24 (2.6% infertile) • Age 30-34 decrease by 15-19 % (11% infertile) • Age 35-39 decrease by 26-46% (33% infertile) • Age 40-45 decrease by 95% (87% infertile) • Data confirmed by insemination studies

Age: IVF • Younger than 35: 42% Live birth per embryo • Age 35-37: 35.1% Live birth per embryo • Age 38-40: 25% Live birth per embryo • Age 41-42: 14.5% Live birth per embryo • Age 43: 5.9% Live birth per embryo • Greater than 43: 2.9% Live birth per embryo

Age: Miscarriage • Recognized • Age 30: 7-15% • Age 31-34: 17-21% • Age 35-39: 17-28% • Age 40: 40-52% • Unrecognized: 60%

What is the mechanism of age that causes infertility?

Physiology of Aging Ovary

Why are older women Infertile? • They less eggs develop? • They ovulate less? • They produce less steroids? NO NO NO

Chromosomes:Aneuploidy • Young women 10% eggs are aneuploidic • Age 40: 30% abnormal • Age 43: 50 % abnormal • Age 45: 100% abnormal

How does one check for ovarian reserve?

Checking for Ovarian Reserve • Success of IVF: the outcome • Physiology : age related increase of FSH • Day 3 FSH: >10-15 mIu/mL • Day 3 Estradiol: >80 pg/mL • Clomiphene Challenge Test (CCT) • Day 3 & Day 10 FSH (after clomid 50mg day 5-9) • IVF success <10%

Who to Screen? • Age >35 • Family Hx POF • Ovarian Surgery • Smoking • Poor Gonadotropin response

Infertility: Guiding Principles • Identify the cause • Provide accurate information • Emotional Support; RESOLVE group • Guide treatments

What life style behaviors decrease infertility?

Basic Info: Life style • 62% of US have BMI > 25 • 25% female in US smoke: 13% infertile • Mary Jane factor • ETOH • Caffeine??

Normal Reproductive Efficiency • Fecundity: baboons 80% Human 20% • 93% of couples pregnant in 2 years • Egg 12-14 hrs, Sperm 3-5 days

How can we help? • Assume day before temp spike on BBT • Peak fertility 2 days prior to ovulation • LH detection • But easiest: Intercourse Twice a week

When should a work-up begin? • Most people need no treatment • 3 year rule • 5% decrease per year in age • 15-25% per year of infertile • >35 don’t wait • Obvious reasons

History & Physical Exam • G’s P’s and complicaion • LNMP, Sexual Activity • Surgery’s • Meds, symptoms • FmHX menopause, reproductive

Physical Exam: • BMI • Thyroid • Skin • Breast • Pelvic

Screening Test • PAP, STD • Rh, Cystic Fibrosis,Rubella • Varicella

What are the main causes of infertility?

Infertility: Causes

Infertility: KISS it • Sperm in cervix • Mature Oocyte • Cervix must nurture sperm • Capture the oocyte in tube • Uterus enviroment

How do we screen for male infertility?

Male Factor

How do we check for ovulatory defects?

Infertility: Ovarian Factor • Menstrual History: 97.7% predictor • BBT • Thermogenic potential of progesterone (.4-.8) • Ovulation when see rise (1-5 days after) • 12 or more days to menses • Progesterone 3-4 ng/mL • 7-8 days post ovulation • Luteal pahse function

Ovulatory Factor • LH excretion: Ovulation prediction (24-48 h) • Start 2-3 days before LH Surge • Late afternoon testing, Concentrate urine • Day of surge and next 2 • Ultrasound

How do we check for tubal factor?

Tubal Factor • Risk factors • PID; 12%,24%,75%, Ectopic 6 fold • HSG • 2-5 days after menses • 1-3 % infection rate high risk • Increase preg rate • False positive obstruction rate (15-30%)

Hydrosalpinges Myoma Normal HSG

Tubal Factor: Laparoscopy • Chromotubation with indigo carmine • Why not methylene blue? • Possibility of Treatment • Tubal surgery: Is it worth it??

Tubal Factor: Chlamydia Antibody testing • Pretest: Laparoscope or not • HSG sooner than latter • Not yet defined

Uterine Factors • Hysterosalpingography (HSG) • HSG v Hysterscope: Sens 98%, Spec 35% • All polyp vs submucous myomas • Ultrasound/Sonohysterography • SIS 75 sens, spec 90%

Polyp Bicornate Mid secr Late Prolif Early Prolif

Endometrial Biopsy Proliferative Secretory

Uterine Factors: Bottom Line Congenital Malformation Leiomyomas Intrauterine Adhesions Endometrial Polyps Yes, Septum only Maybe, submucous Yes Maybe

Cervical Factor • Postcotial test (Sims-Huhner) Intercourse (2-12 hrs) for test Look at: pH, Sperm, Spinnbarkeit, Ferning Cellularity, Sperm Shaking, sperm Agglutanation Has seen better days

Unexplained Infertility • Defined • 10-30% incidence • Laparoscope necessary: • Canadian Study: 17% v 29% (NTT:9) • Just slower to get pregnant 3 year data • Spontaneous conception falls 40%

UI:Who should you treat?

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Causes of Female Infertility

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Female Infertility Centre in India

Manipal Fertility is a leading female infertility centre in India. We are providing the best female infertility treatment at very low cost with high success rates. To know more just you can visit at http://manipalfertility.com/our-services/female-infertility

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Female Infertility treatment

In every 10 couples, 3 pairs may have a fertility problem. Simply the blame goes on the women. But, The truth is infertility can be an issue for either partner. Homeopathy is the simple solution to come out of fertility problems for both. Homwopathy is the safe way to treat Infertility problems because natural substance won't cause any side-effects. Homeocare International is providing both Male infertility homeopathy treatment & Female Infertility treatment with best results since 1986. Visit www.homeocare.in to know more.

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Female infertility due to smoking

Smoking can seriously impair the normal functioning of the female reproductive organs right from hindering the proper working of the ovaries to adversely affecting the healthy environment in the uterus. Female egg quality is seriously hampered in smoking women. Smoking also affects the DNA of the egg which could result in malformation of the embryo.

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What Cause Infertility In Female?

Female infertility cases are rising in India. There are various causes behind the occurrence of female infertility. People often ask one question – ‘What Cause Infertility in Female?’ There are different reasons for female infertility. Here we have discussed some of those reasons.

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Truth behind Female Infertility

The reasons of infertility can range. Most normally, ladies who're infertile suffer from ovulation disorders, damaged fallopian tubes, cervical blockage, and some of other fitness troubles which could result in infertility.

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female infertility treatment in hyderabad

There is no unanimous definition of female infertility, because the definition depends on social and physical characteristics which may vary by culture and situation. NICE guidelines state that: "A woman of reproductive age who has not conceived

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Female Infertility Treatment | Female Infertility | IVF Female Infertility | Elawoman

Barrenness is the inadequacy to get pregnant following a time of unprotected intercourse. Both male and female can be in charge of fruitlessness. Discussing fruitlessness in ladies, Female Infertility Treatment is crucial for them who are endeavoring to get pregnant yet are as yet unsuccessful in spite of for over a time of unprotected intercourse. Along these lines it is indispensable for couples to look for appropriate medicinal help.

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Treatment of Female Infertility

Health treatment

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Female Infertility Treatment in Hyderabad

Sridevi Fertility is best IVF Centre in Hyderabad, get treated for all your fertility problems with best female fertility specialist in Hyderabad – Dr.Swetha Thumula. Female infertility treatments at Sridevi Fertility hospital enables patients to have convenient and painless fertility treatment.

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What Cause Female Infertility ?

The infertility problem may be caused by either female or male or both. But most of this problem is raised in the female because she is getting pregnant.

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Female Infertility Treatment Haryana

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Female Infertility Treatment Meerut

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Female Infertility Treatment in Hyderabad, Female Infertility Doctors in Hyderabad -Sridevi Fertility

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Female Infertility

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Obesity Affect Female Infertility

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Hyperthyroidism and female infertility

One of the important causes of female infertility is hyperthyroidism. It is a disorder of the thyroid gland which is overactive. Many females suffer from this condition and thereby they can also suffer from infertility conditions which they only get to acknowledge after they try to conceive for years and fail to achieve the same. https://www.progenesisivf.com/blog/hyperthyroidism-and-female-infertility/

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Ayurvedic Treatment for Female Infertility problems. This package boosts fertility in females curing also other problems that are causing infertility problems in women.

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With over 6 million presentation templates available for you to choose from, crystalgraphics is the award-winning provider of the world’s largest collection of templates for powerpoint and google slides. so, take your time and look around. you’ll like what you see whether you want 1 great template or an ongoing subscription, we've got affordable purchasing options and 24/7 download access to fit your needs. thanks to our unbeatable combination of quality, selection and unique customization options, crystalgraphics is the company you can count on for your presentation enhancement needs. just ask any of our thousands of satisfied customers from virtually every leading company around the world. they love our products. we think you will, too" id="category_description">crystalgraphics creates templates designed to make even average presentations look incredible. below you’ll see thumbnail sized previews of the title slides of a few of our 15 best infertility templates for powerpoint and google slides. the text you’ll see in in those slides is just example text. the infertility-related image or video you’ll see in the background of each title slide is designed to help you set the stage for your infertility-related topics and it is included with that template. in addition to the title slides, each of our templates comes with 17 additional slide layouts that you can use to create an unlimited number of presentation slides with your own added text and images. and every template is available in both widescreen and standard formats. with over 6 million presentation templates available for you to choose from, crystalgraphics is the award-winning provider of the world’s largest collection of templates for powerpoint and google slides. so, take your time and look around. you’ll like what you see whether you want 1 great template or an ongoing subscription, we've got affordable purchasing options and 24/7 download access to fit your needs. thanks to our unbeatable combination of quality, selection and unique customization options, crystalgraphics is the company you can count on for your presentation enhancement needs. just ask any of our thousands of satisfied customers from virtually every leading company around the world. they love our products. we think you will, too.

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Health specialists say biased Medicare rebates are costing women more

Women's health specialists say gender bias in rebates for medical procedures is costing women more money and disincentivising women's health practitioners.

Gynaecologists, obstetricians and midwives are calling for an urgent gender review of the Medicare Benefits Schedule, alleging inequality in how procedures are subsidised for women compared to those provided for men.

They say unequal rules are also cutting women out of eligibility for certain procedures despite them being available for men.

Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) vice president Nisha Khot said there were unfair rebates across the board.

"What the Medicare Benefits Schedule shows us very clearly is that there is a Medicare gap between what is reimbursed for women and what is reimbursed for men," she said.

How the Medicare rebate works

Medical procedures, consultations and diagnostic services are listed on the MBS, with the government setting a recommended fee for those items.

The government then pays a percentage of that recommended fee to the patient to help cover treatment costs.

But doctors and clinics can charge the patient more than that fee, particularly if the costs of performing the treatment outstrip the recommended price, with the gap covered by the patient.

The subsidies are determined based on who provides the service: 100 per cent for GP services, 85 per cent for out-of-hospital services and 75 per cent for private patients in hospitals.

When the government recommended fee is higher, so is the rebate paid to the patient.

One example highlighted to the ABC is the subsidy for vasectomies compared to IUD insertion.

Vasectomies typically take 15-20 minutes, with one small cut made on each side of the scrotum.

By comparison, IUD insertion typically takes 30-45 minutes with doctors highlighting the costs of needing an assistant, recovery room and a number of specialist tools.

Despite this, the cost is set lower by the government, meaning women often have to pay a larger gap, because GPs and specialists need to charge more to cover their costs.

The Health Department's Medical Costs Finder reports patients typically paid $427 after a $203 rebate for a vasectomy, and typically paid $85 after a $47 rebate for an IUD insertion.

Labour intensive procedures

Dr Khot, a practising obstetrician at Peninsula Health in Victoria, cited female internal pelvic ultrasounds compared to scrotal ultrasounds as another example.

"The pelvis contains the uterus, it contains the neck of the uterus, which is the cervix, it contains the bowel, it contains all of the attachments of the uterus to the side walls of the pelvis, it contains the bladder … which means that these scans take time, they take expertise, but they definitely should have a higher Medicare rebate than a scan that doesn't require that level of expertise or that amount of time," Dr Khot said.

She said the disparity also affects pregnant women.

"We're scanning the baby looking for abnormalities of various organs, so it's literally a top-to-toe scan of the baby while it is still within mother's tummy, so it is a complex scan," Dr Khot said.

"A scrotal scan is looking at one organ, which is easily seen and doesn't need to have a huge deal of time or expertise when you're looking just at one organ versus looking at a baby with multiple organs, where you're trying to make sure that every single organ is developing the way [it] should."

Dr Khot said having lower rebates for these kinds of procedures was also a disincentive for more doctors to enter the specialties of gynaecology and obstetrics, because it is harder to afford to run a practice.

On top of rebates for procedures, Dr Khot said there was also no specific rebate available for extended gynaecology appointments.

"Increasingly, what we know is that [for] conditions, especially conditions that have chronic pelvic pain … women will have a range of different symptoms, and need to have those extended appointments at which they can have discussions with the doctor."

Gender inequity 'baked into the system'

Sarah White, chief executive of women's health organisation Jean Hailes, said even when a Medicare rebate amount is the same for men and women, there can be unfair rules about how it's applied.

She pointed to bone scans for cancer patients whose treatment has caused hypogonadism — when ovaries or testes aren't producing enough oestrogen or testosterone.

The condition can cause infertility, tiredness and mood swings among other symptoms.

Men can access the rebate at any age, while women must have the condition for six months and must be under 45 years (although there are exceptions for women receiving steroid treatment).

And that's despite women being the subject of 82 per cent of procedures under this item.

"Women in that circumstance have a higher risk of having a fracture than men … if you're bloke, you can have it at any time even though your risk is lower, but if you're a woman, there's all sorts of caveats," Ms White said.

"We have these inequities just baked into the system.

"There has to be a review that's not just based on an indication for a man versus indication for a woman, there has to be an assessment of some equity in there."

Ms White said she wants Health Minister Mark Butler to "put his weight behind this", and is calling for a bipartisan approach to overhaul the system.

Alison Weatherstone, chief midwife at the Australian College of Midwives, also wants Mr Butler to carry out a review for how midwives, a profession dominated by women, claim rebates.

"One really great example of that is the postnatal visit, which the midwife can only claim a combined mother and baby appointment, even though there's been an assessment performed on both," she said.

"Whereas if you go to a medical practitioner, they can separately claim for both the mother and baby individually.

"We are providing twice the amount of work for the single revenue, so it's definitely inequitable."

Mr Butler would not be drawn on whether he backed a specific Medicare gender review but said there was real, structural bias in the system.

"We're very clear as we came into the election that we were concerned about quite a structural bias in the healthcare system," he said.

"We've got some really good work under way, really very deliberately looking through those things that women, very understandably, complain about in terms of their experience in the healthcare system.

"We'll do absolutely what we can to address the inequalities."

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