Gynecology Topic 11. Examinations and treatment in infertility

I. Initial Evaluation of the Infertile Couple

General Principle

• Infertility is a couple diagnosis → evaluate both partners in parallel.
• Work-up usually starts with low-invasive, high-yield tests: semen analysis, ovulation assessment, uterine/tubal assessment.

General Anamnesis

• Medical history: liver/renal disease, thyroid disease, hypertension, diabetes, autoimmune disease, cancer therapy.
• Gynecologic history: cycle regularity, dysmenorrhea, dyspareunia, PID, endometriosis, abnormal bleeding.
• Surgical history: previous laparotomy, pelvic surgery, gynecologic operations, curettage, tubal surgery.
• Obstetric history: delivery, miscarriage/abortion, ectopic pregnancy, stillbirth, postpartum infection.
• Male/lifestyle history: cryptorchidism, orchitis, torsion, varicocele, surgery, erectile/ejaculatory dysfunction, heat/toxin/drug exposure, smoking, alcohol, BMI.

II. Female Investigations

Ovarian / Ovulatory Factor

• Basal body temperature: biphasic curve suggests ovulation; monophasic curve suggests anovulation.
• Urine LH test: detects LH surge before ovulation → timing intercourse/insemination.
• Hormones: FSH, LH, estradiol, progesterone, testosterone/DHEA-S, TSH, prolactin.
• Pelvic US: ovarian morphology, follicles, follicle monitoring, uterine/adnexal pathology.

Tubal and Uterine Factor

• Hysterosalpingography (HSG): X-ray + intrauterine contrast → uterine cavity shape + tubal patency; spill into peritoneal cavity suggests patent tubes.
• Sonohysterography/HyCoSy: ultrasound-based cavity/tubal assessment with saline or contrast.
• Hysteroscopy: direct examination of uterine cavity → polyps, submucosal fibroid, septum, adhesions; allows treatment.
• Laparoscopy with chromopertubation: methylene blue/contrast through cervix → direct tubal patency assessment; also detects/treats endometriosis and adhesions.

III. Male Investigation

Semen Analysis

• First-line male test; repeat if abnormal.
• Assess: semen volume, sperm count/concentration, motility and morphology.
• Normal lower reference values: volume >= 1.5 mL, concentration >= 15 million/mL, total motility about >= 40%, normal morphology >= 4%.

Semen Abnormalities

• Aspermia: no semen.
• Hypospermia: low semen volume, classically < 1.5 mL.
• Azoospermia: no sperm in semen.
• Cryptozoospermia: extremely low sperm count, sperm found only after centrifugation or repeated analysis.
• Oligozoospermia: low sperm concentration, classically < 15 million/mL.
• Asthenozoospermia: decreased motility <40%.
• Teratozoospermia: abnormal morphology; strict normal morphology <4% is abnormal.

IV. Treatment and Assisted Reproduction

Timed Intercourse

• Predict ovulation: urine LH test, basal temperature, cycle tracking.
• Advice: daily or every 1-2 days starting about 5 days before expected ovulation until ovulation.

Ovulation Induction / Ovarian Stimulation

• Clomiphene citrate: SERM/antiestrogen → blocks hypothalamic estrogen feedback → increased GnRH/FSH → follicle recruitment and ovulation.
• Letrozole: aromatase inhibitor; current common first-line for PCOS-related anovulatory infertility.
• Gonadotropins: hMG/FSH or recombinant FSH → controlled follicle growth; hCG triggers final oocyte maturation/ovulation.
• GnRH agonist/antagonist: prevents premature LH surge during controlled ovarian stimulation.
• Monitoring: transvaginal US ± estradiol → follicle number/size, reduce multiple pregnancy and OHSS risk.

Intrauterine Insemination and Surgery

• Intrauterine insemination (IUI): prepared concentrated sperm introduced into uterine cavity around ovulation.
• Indications: mild male factor, hostile cervical mucus, sexual/ejaculatory difficulty, unexplained infertility.
• Often combined with ovulation induction to improve success.
• Surgical treatment: correct anatomical causes, e.g. leiomyoma, endometriosis, adhesions, tubal disease.

IVF-ET: Main Steps

1. Ovarian stimulation: FSH/hMG injections → multiple follicular development; GnRH agonist/antagonist prevents premature ovulation.
2. Monitoring and trigger: transvaginal US; hCG or GnRH agonist trigger when follicles are mature, classically around 18 mm.
3. Oocyte retrieval: transvaginal US-guided follicle aspiration.
4. Sperm collection: semen sample or testicular tissue/sperm retrieval if severe male factor.
5. Fertilization: conventional IVF = oocytes + sperm co-incubated; ICSI = one sperm injected into oocyte.
6. Embryo culture: day 2 about 4 cells, day 3 about 8 cells, day 5 blastocyst.
7. Embryo transfer: ultrasound-guided soft catheter into uterine cavity; surplus embryos may be cryopreserved.

Genetic Testing

• Preimplantation genetic testing: embryo testing before transfer for selected genetic/chromosomal indications.
• Used for selected monogenic disease, chromosomal rearrangement or aneuploidy-risk situations according to local policy.

Complications of IVF

• Ovarian stimulation: ovarian cysts, OHSS, multiple pregnancy risk.
• Oocyte retrieval: infection/PID, bleeding, vascular injury, bowel injury.
• Embryo transfer/pregnancy: ectopic pregnancy, spontaneous abortion, multiple pregnancy.

Ovarian Hyperstimulation Syndrome

• Mechanism: hCG exposure + many corpora lutea → VEGF release → increased vascular permeability → third spacing.
• Symptoms: abdominal distension/pain, nausea, vomiting, enlarged ovaries, ascites, dyspnea/pleural effusion, oliguria/anuria.
• Risks: hemoconcentration, electrolyte disturbance, renal/liver dysfunction, thromboembolism.
• Treatment: fluids (PO if mild, IV if severe), monitor Hct/electrolytes/liver/renal function/urine output, paracentesis if tense ascites/effusion, thromboprophylaxis, avoid further hCG exposure.