The WHO's 2025 Infertility Guideline: What Changed and Why It Matters

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.

Age is the dominant factor. Citing the US SART and UK HFEA registries, Dr. Pai gave approximate success rates by age band: under 35 about 40%, 35 to 37 roughly 35 to 40%, 37 to 39 about 25 to 30%, 39 to 41 about 15%, and over 41 about 5 to 10%, because genetic abnormality rates in eggs rise with age even when embryos form. Low ovarian reserve, with AMH sometimes as low as 0.3 to 0.4 ng/ml, is the other major factor; for patients who decline donor eggs, he tries platelet-rich plasma injected under ultrasound or laparoscopic guidance and, in some cases, stem-cell therapy, using the laparoscopy to also rule out genital tuberculosis, which can itself lower ovarian reserve.

Ayushman Bharat, India's national health scheme, does not yet cover infertility treatment, though several Indian state governments now subsidise IVF, a pattern expected to spread to more African governments as awareness grows.

WHO names five audiences: policymakers at national and sub-national level, healthcare professionals including physicians, nurses, embryologists and midwives, professional societies such as FIGO and national federations, patient advocacy groups, and funding and philanthropic bodies.

Out-of-pocket cost currently excludes poorer patients from infertility care almost everywhere, so the guideline asks health systems to integrate it into universal health coverage rather than treat it as a separate, self-funded service.

Despite roughly half of all cases involving a male factor, women are more often blamed, and 36 percent of women affected by infertility report exposure to intimate partner violence as a consequence.