Causes of female infertility
- Wendy Kuohung, MD
Wendy Kuohung, MD
- Associate Professor of Obstetrics and Gynecology
- Boston University School of Medicine
- Mark D Hornstein, MD
Mark D Hornstein, MD
- Professor of Obstetrics, Gynecology & Reproductive Biology
- Harvard Medical School
Infertility is a complex disorder with significant medical, psychosocial, and economic aspects. The etiologies of female infertility will be reviewed here. Evaluation and treatment of female infertility are discussed separately. (See "Evaluation of female infertility" and "Treatments for female infertility".)
Causes of male infertility are also discussed elsewhere. (See "Causes of male infertility".)
In a World Health Organization (WHO) study of 8500 infertile couples, female factor infertility was reported in 37 percent of infertile couples in developed countries, male factor infertility in 8 percent, and both male and female factor infertility in 35 percent . The remaining couples had unexplained infertility or became pregnant during the study. The most common identifiable female factors, which accounted for 81 percent of female infertility, were:
●Ovulatory disorders (25 percent)
●Endometriosis (15 percent)
- WHO Technical Report Series. Recent Advances in Medically Assisted Conception Number 820, 1992, pp 1-111.
- American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril 2014; 101:633.
- Baker TG. Radiosensitivity of mammalian oocytes with particular reference to the human female. Am J Obstet Gynecol 1971; 110:746.
- Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 1987; 65:1231.
- Faddy MJ, Gosden RG. A mathematical model of follicle dynamics in the human ovary. Hum Reprod 1995; 10:770.
- Jick H, Porter J. Relation between smoking and age of natural menopause. Report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center. Lancet 1977; 1:1354.
- Cramer DW, Barbieri RL, Xu H, Reichardt JK. Determinants of basal follicle-stimulating hormone levels in premenopausal women. J Clin Endocrinol Metab 1994; 79:1105.
- Westhoff C, Murphy P, Heller D. Predictors of ovarian follicle number. Fertil Steril 2000; 74:624.
- Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr Rev 2009; 30:465.
- Legendre G, Catala L, Morinière C, et al. Relationship between ovarian cysts and infertility: what surgery and when? Fertil Steril 2014; 101:608.
- Practice Committee of the American Society for Reproductive Medicine. Committee opinion: role of tubal surgery in the era of assisted reproductive technology. Fertil Steril 2012; 97:539.
- Pritts EA. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv 2001; 56:483.
- Homer HA, Li TC, Cooke ID. The septate uterus: a review of management and reproductive outcome. Fertil Steril 2000; 73:1.
- Practice Committee of the American Society for Reproductive Medicine. Current clinical irrelevance of luteal phase deficiency: a committee opinion. Fertil Steril 2015; 103:e27.
- Balasch J, Fábregues F, Creus M, Vanrell JA. The usefulness of endometrial biopsy for luteal phase evaluation in infertility. Hum Reprod 1992; 7:973.
- Coutifaris C, Myers ER, Guzick DS, et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 2004; 82:1264.
- Casadei L, Puca F, Privitera L, et al. Inherited thrombophilia in infertile women: implication in unexplained infertility. Fertil Steril 2010; 94:755.
- Coulam CB, Jeyendran RS. Thrombophilic gene polymorphisms are risk factors for unexplained infertility. Fertil Steril 2009; 91:1516.
- Steinvil A, Raz R, Berliner S, et al. Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilisation. Thromb Haemost 2012; 108:1192.
- Cervera R, Balasch J. Bidirectional effects on autoimmunity and reproduction. Hum Reprod Update 2008; 14:359.
- Bellver J, Pellicer A. Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome. Fertil Steril 2009; 92:1803.
- Hornstein MD, Davis OK, Massey JB, et al. Antiphospholipid antibodies and in vitro fertilization success: a meta-analysis. Fertil Steril 2000; 73:330.
- Practice Committee of American Society for Reproductive Medicine. Anti-phospholipid antibodies do not affect IVF success. Fertil Steril 2008; 90:S172.
- Kallen CB, Arici A. Immune testing in fertility practice: truth or deception? Curr Opin Obstet Gynecol 2003; 15:225.
- Tersigni C, Castellani R, de Waure C, et al. Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms. Hum Reprod Update 2014; 20:582.
- Clementini E, Palka C, Iezzi I, et al. Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques. Hum Reprod 2005; 20:437.
- Christensen RB, Matsumoto AM, Bremmer WJ. Idiopathic hypogonadotropic hypogonadism with anosmia (Kallmann syndrome). Endocrinologist 1992; 2:332.
- de Roux N, Young J, Misrahi M, et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med 1997; 337:1597.
- Layman LC, Cohen DP, Jin M, et al. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat Genet 1998; 18:14.
- Aittomäki K, Lucena JL, Pakarinen P, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 1995; 82:959.
- Phillip M, Arbelle JE, Segev Y, Parvari R. Male hypogonadism due to a mutation in the gene for the beta-subunit of follicle-stimulating hormone. N Engl J Med 1998; 338:1729.
- Toledo SP, Brunner HG, Kraaij R, et al. An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female. J Clin Endocrinol Metab 1996; 81:3850.
- Schwartz CE, Dean J, Howard-Peebles PN, et al. Obstetrical and gynecological complications in fragile X carriers: a multicenter study. Am J Med Genet 1994; 51:400.
- Achermann JC, Meeks JJ, Jameson JL. Phenotypic spectrum of mutations in DAX-1 and SF-1. Mol Cell Endocrinol 2001; 185:17.
- Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387:903.
- Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392:398.
- de Roux N, Genin E, Carel JC, et al. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 2003; 100:10972.
- Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003; 349:1614.
- Dodé C, Levilliers J, Dupont JM, et al. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet 2003; 33:463.
- Feng R, Sang Q, Kuang Y, et al. Mutations in TUBB8 and Human Oocyte Meiotic Arrest. N Engl J Med 2016; 374:223.
- Ovulatory disorders
- Oocyte aging
- Ovarian cysts
- FALLOPIAN TUBE ABNORMALITIES/PELVIC ADHESIONS
- Uterine leiomyomata
- Uterine anomalies
- Luteal phase defect
- CERVICAL FACTORS
- INHERITED THROMBOPHILIA
- IMMUNE FACTORS
- Antiphospholipid syndrome
- Antibodies unrelated to APS
- Celiac disease
- GENETIC CAUSES
- LIFESTYLE FACTORS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS