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PY9.1-10 | Reproductive Physiology — Part 5

Infertility: When the Reproductive System Fails

Causes of Infertility in Couples

Category Proportion Common Causes Key Investigation
Male factor 30-40% Varicocele, azoospermia, oligospermia, hormonal Semen analysis (count, motility, morphology)
Female — ovulatory ~25% PCOS, hypothalamic amenorrhoea, premature ovarian failure Day 21 progesterone, FSH/LH, AMH, ultrasound
Female — tubal ~20% PID, endometriosis, previous ectopic Hysterosalpingography (HSG), laparoscopy
Female — uterine ~10% Fibroids, Asherman's syndrome, congenital anomalies Hysteroscopy, saline infusion sonography
Unexplained 10-15% No identifiable cause after standard workup Empiric treatment: IUI → IVF

Causes of Infertility in Couples

Infertility: When the Reproductive System Fails

Figure: Infertility: When the Reproductive System Fails

Four-panel illustration showing infertility cause distribution in couples, male infertility causes with semen parameters, female infertility causes including ovulatory dysfunction and tubal factors, and the five-step IVF procedure.
Category Proportion Common Causes Key Investigation
Male factor 30-40% Varicocele, azoospermia, oligospermia, hormonal Semen analysis (count, motility, morphology)
Female — ovulatory ~25% PCOS, hypothalamic amenorrhoea, premature ovarian failure Day 21 progesterone, FSH/LH, AMH, ultrasound
Female — tubal ~20% PID, endometriosis, previous ectopic Hysterosalpingography (HSG), laparoscopy
Female — uterine ~10% Fibroids, Asherman's syndrome, congenital anomalies Hysteroscopy, saline infusion sonography
Unexplained 10-15% No identifiable cause after standard workup Empiric treatment: IUI → IVF

Causes of Infertility in Couples

Category Proportion Common Causes Key Investigation
Male factor 30-40% Varicocele, azoospermia, oligospermia, hormonal Semen analysis (count, motility, morphology)
Female — ovulatory ~25% PCOS, hypothalamic amenorrhoea, premature ovarian failure Day 21 progesterone, FSH/LH, AMH, ultrasound
Female — tubal ~20% PID, endometriosis, previous ectopic Hysterosalpingography (HSG), laparoscopy
Female — uterine ~10% Fibroids, Asherman's syndrome, congenital anomalies Hysteroscopy, saline infusion sonography
Unexplained 10-15% No identifiable cause after standard workup Empiric treatment: IUI → IVF

Infertility is defined as the failure to achieve a clinical pregnancy after 12 months of regular, unprotected sexual intercourse (or 6 months if the woman is >35 years old). It affects ≈10–15% of couples in India.

Infertility: When the Reproductive System Fails

Figure: Infertility: When the Reproductive System Fails

Four-panel illustration showing infertility cause distribution in couples, male infertility causes with semen parameters, female infertility causes including ovulatory dysfunction and tubal factors, and the five-step IVF procedure.

Causes in couples (approximate distribution):
• Male factor alone: 30–40%
• Female factor alone: 30–40%
• Combined: 20–30%
• Unexplained: 10–15%

Male causes:
Azoospermia (no sperm): obstructive (blocked vas deferens — post-vasectomy, post-infection) or non-obstructive (spermatogenic failure)
Oligospermia (<15 million/mL): varicocele, hormonal causes, cryptorchidism (undescended testis → higher temperature → impaired spermatogenesis)
Asthenospermia (poor motility): oxidative stress, infection
Hypogonadism: low testosterone → low FSH/LH (hypothalamic/pituitary cause) or primary testicular failure

Female causes:
Ovulatory dysfunction (25–30% of female infertility): PCOS (most common), hypothalamic amenorrhoea, premature ovarian insufficiency (POI), hyperprolactinaemia (prolactin inhibits GnRH)
Tubal factor (20–30%): blocked fallopian tubes from PID (pelvic inflammatory disease), endometriosis, prior ectopic pregnancy, surgical adhesions
Uterine/cervical: fibroids (submucosal), polyps, cervical stenosis, Asherman syndrome (intrauterine adhesions)
Endometriosis: ectopic endometrial tissue → inflammation, adhesions, tubal occlusion

IVF — In Vitro Fertilisation:
Indications: tubal factor, severe male factor (with ICSI), unexplained infertility, failed other treatments, same-sex couples
Steps:
1. Ovarian stimulation: FSH injections (controlled ovarian hyperstimulation, COH) → multiple follicles develop
2. Oocyte retrieval: transvaginal ultrasound-guided aspiration of mature follicles (under sedation) → multiple eggs collected
3. Fertilisation: eggs incubated with prepared sperm in vitro; or ICSI (intracytoplasmic sperm injection — single sperm injected directly into egg)
4. Embryo culture: fertilised eggs cultured 2–5 days to blastocyst stage
5. Embryo transfer: 1–2 embryos transferred into uterine cavity; remaining embryos cryopreserved
6. Luteal support: progesterone supplementation until placenta takes over
Success rate: ≈35–40% live birth per cycle in women <35 years; declines with age
Complications: ovarian hyperstimulation syndrome (OHSS), multiple pregnancy

CLINICAL PEARL

Prolactin and Infertility:
Hyperprolactinaemia is a common, easily missed cause of infertility. Elevated prolactin (from a prolactinoma — a benign pituitary adenoma, or from hypothyroidism/drugs) suppresses GnRH → suppresses FSH + LH → anovulation + amenorrhoea.

Key point: always check serum prolactin in any woman with irregular periods or unexplained infertility, especially if she has galactorrhoea (milk secretion outside pregnancy/breastfeeding).

Treatment: cabergoline or bromocriptine (dopamine agonists — inhibit prolactin secretion). Most prolactinomas shrink without surgery.

SELF-CHECK — Part 5 Self-Check

A 50-year-old woman has FSH = 85 IU/L and her last period was 14 months ago. The most likely diagnosis is:

A. Premature ovarian insufficiency

B. PCOS

C. Menopause

D. Hypothalamic amenorrhoea

Reveal Answer

Answer: C. Menopause


Which investigation is MOST useful to diagnose ovulatory dysfunction as a cause of infertility?

A. Day 2–3 serum FSH and oestradiol

B. Mid-luteal phase (Day 21) serum progesterone

C. Transvaginal ultrasound on Day 1

D. Serum testosterone

Reveal Answer

Answer: B. Mid-luteal phase (Day 21) serum progesterone