Diagnosis and Management of the Infertile Couple

Ozempic is semaglutide. Untreated obesity itself carries heart, kidney, liver, joint and psychological risks that dwarf the drug's own side effects, which Dr. Pai compared to the rare risk of a plane crash or of liver failure from paracetamol, neither of which stops those products being used. He attributed the outsized scrutiny to how much public attention weight-loss drugs attract, not to an unusual risk profile compared with other common medications such as blood pressure drugs.

These drugs are not used during pregnancy. Dr. Pai's protocol is to bring the patient's weight down, stop the drug, wait about a month for it to wash out, then begin ovarian stimulation, retrieve eggs, freeze embryos, and transfer roughly a month later. He noted that around 50,000 unplanned pregnancies occurred among women on Ozempic in the US with no reported harm, and drew a parallel to metformin, once considered risky in pregnancy and now used throughout it.

Clomiphene 50 mg twice daily from day 2 to day 6, plus HMG 150 IU on days 7 and 9. HMG is avoided in PCOS patients because of hyperstimulation risk; PCOS is diagnosed by an antral follicle count above 15 with a necklace pattern on ultrasound and a high AMH, which Dr. Pai called their gold-standard test. He also recommends AMH testing for daughters to check ovarian reserve, with egg freezing considered before age 35 if a woman is not yet married.

Most commonly amenorrhoea or very scanty periods, occasionally heavy bleeding. Diagnosis relies on TB-PCR and D&C with histopathology, but because PCR can be falsely negative, Dr. Pai prefers laparoscopy for direct visual confirmation, alongside a chest X-ray, palpation of cervical and groin lymph nodes, family history, sputum AFB testing on three consecutive days where indicated, interferon-gamma release assays and a Mantoux test. Treatment is AKT-4 for two months followed by AKT-2 continuation therapy, nine months in total, which must be completed fully to avoid multidrug-resistant TB; laparoscopy and hysteroscopy are repeated afterward before trying IUI, and IVF only if that fails.

WHO's pathway is stepwise: rule out anovulation with day-21 progesterone above 10 ng/ml, rule out tubal block with an HSG, rule out uterine factors with 2D or 3D ultrasound, and test semen; if all are normal, try timed intercourse with clomiphene for 3 to 6 months, then 2 to 3 cycles of IUI (up to 6 if needed), which Dr. Pai's practice sees succeed in about 30% of cases, before moving to IVF. He named failure to conceive as IVF's biggest drawback, though across three attempts roughly 80 to 90% of patients achieve pregnancy, and frozen-embryo banking means most repeat cycles no longer require re-stimulation. In his estimate, about 80% of patients never need IVF at all if laparoscopy, hysteroscopy, ultrasound and a competent IUI lab are available; only 20% require it.

WHO reviewed 12,241 research papers published between 1990 and 2021 and found that infertility affects 17.5 percent of people of reproductive age, not the 5 percent long assumed in clinical teaching.

Select diagnostic tests based on clinical findings, listen to the couple and respect their preferences, base treatment on benefits, harms, values, feasibility and cost, consider cost-effectiveness, discuss follow-up and risk, and document pregnancy outcomes.

Early evaluation after six months rather than twelve is warranted when the woman is 35 or older, when known risk factors are present, or when cycles are irregular or there is a history of pelvic infection.

The 2025 document, while landmark, omits several conditions that dominate his own caseload: diagnostic laparoscopy and hysteroscopy, genital tuberculosis, endometriosis, fertility preservation and azoospermia management, a gap attributed partly to guideline committees that under-represent clinicians practising in Asia, Africa and Latin America.