Female infertility

Definition

When to Investigate

• Definition of sterility: no conception after 12 months.
• Age at which to start earlier: from age 35 (declining oocyte reserve).
• Primary vs. secondary sterility: primary: never been pregnant.

• Infertility denotes failure to conceive despite regular unprotected intercourse for 12 months, or for 6 months in women older than 35.
• With frequent unprotected intercourse, about 70% of couples conceive within 3 months, 80% within 6 months and 90% within one year.

Classification

• By cause, sperm disorders, ovulatory dysfunction, diminished ovarian reserve, tubal factors, endometriosis, uterine or other pelvic abnormalities, cervical factors and unexplained infertility are distinguished.

Occurrence & epidemiology

Epidemiology

• Up to 15% of couples worldwide are affected.
• A male factor, alone or together with a female factor, is involved in about half of cases.

Aetiopathogenesis

Sorting the Causes

• Uterine causes: fibroids, polyps, synechiae, septa.
• Endocrine causes: PCOS, hyperprolactinemia, thyroid disease.
• Peritoneal cause: endometriosis/adenomyosis with adhesions.

Aetiology and pathogenesis

• Ovulatory dysfunction accounts for about 21–25% of cases; polycystic ovary syndrome is the most common cause of anovulatory infertility (up to 80%), others being hyperprolactinaemia, functional hypothalamic amenorrhoea and thyroid dysfunction.
• Ovarian reserve is often diminished beyond the age of 35, with an accelerated decline around 37–38; endometriomas, pelvic infections, smoking and obesity can also reduce it.
• Tubal factors (11–67% of cases) can arise from fibrosis and tubal occlusion after salpingitis in the setting of pelvic inflammatory disease.
• Uterine causes include leiomyomas, endometrial polyps and intrauterine adhesions (Asherman syndrome); endometriosis is reported as the cause in 6–40% of cases.
• Smoking and excessive alcohol or caffeine consumption can impair fertility; in 15–28% the cause remains unexplained.

Clinical features

More facts from the study questions

• The investigation includes genetic causes (karyotyping) and anatomical uterine factors in addition to coagulation.
• Investigating for antiphospholipid syndrome is a key part of coagulation screening for recurrent miscarriage.
• The definition of recurrent miscarriage is the occurrence of three or more consecutive miscarriages.
• Measurement of thyroid (TSH) and prolactin levels is not cycle-dependent.
• They are part of the basic work-up for subfertility.
• Proof of ovulation is established by the rise in progesterone during the luteal phase.
• The measurement is typically taken around day 21 of the cycle.
• Laparoscopy with chromopertubation is a procedure to check fallopian tube patency.
• An alternative, less invasive method is contrast-enhanced sonography.
• Basal hormone diagnostics (FSH, LH, oestradiol, testosterone, AMH) are performed at the beginning of the cycle.

• The leading symptom is the unfulfilled wish for a child, frequently accompanied by anxiety, sadness, guilt and sometimes depression.
• Clues to the cause include menstrual irregularities, signs of hyperandrogenism such as hirsutism or acne, and uterine or adnexal findings such as leiomyomas or endometriomas.

Diagnosis

In the Woman

• Hormone lab tests on the correct day: FSH, LH, E2, testosterone, AMH on day 2–5.
• Measured regardless of the cycle day: TSH and prolactin.
• Proof of ovulation having occurred: progesterone rise in luteal phase (approx. day 21).
• What is looked for on ultrasound: fibroids, polyps, adenomyosis, uterine anomaly.
• Checking tubal patency: laparoscopy with chromopertubation.

In the Man

• Basic investigation: semen analysis per current WHO criteria.
• Proportion of male causes: approx. 1/3, plus 1/3 combined causes.

• A serum progesterone of at least 3 ng/mL about one week before the next menstrual period indicates that ovulation has occurred; the basal body temperature chart is often inaccurate.
• Ovarian reserve is assessed most sensitively by AMH and the antral follicle count on ultrasound, as FSH rises only late; TSH and prolactin are measured when cycles are disturbed.
• Tubal patency is assessed by hysterosalpingography, sonography with intrauterine fluid instillation or laparoscopy; laparoscopy is considered the gold standard for tubal abnormalities.
• The uterine cavity is first assessed by transvaginal ultrasound; hysteroscopy is the gold standard for intrauterine pathology.
• Because about half of cases involve a male factor, both partners are evaluated, the man with semen analysis.

Keep learning in the app

Further reading (selection)

1. MSD Manual Professional: Overview of Infertility
2. MSD Manual Professional: Ovulatory Dysfunction
3. Primer on Female Infertility for the Reproductive Urologist (Urol Res Pract 2023, PubMed Central)
4. DocCheck Flexikon, Sterilität
5. DocCheck Flexikon, Spermiogramm

Cross-references