Director, Fortis Bloom IVF Centre, Fortis Bloom IVF Centre
Part 6 of 13 in Diagnosis and Management of Infertile Couple - Latest Guidelines by WHO
Weight-Loss Pharmacotherapy in Fertility Care: Semaglutide and Tirzepatide
August 28, 2026
Obesity reduces the odds of a successful pregnancy at every stage of fertility treatment, and roughly 30 percent of the population, in Dr. Pai's estimate, is now affected. His masterclass spent nearly as much time on weight-loss pharmacology as on any single fertility diagnosis, a reflection of how central it has become to his practice.
Three drug classes, one underlying mechanism
GLP-1 agonists such as semaglutide were the first to market and remain the most established, having been used in the United States for roughly a decade. GLP-1/GIP combinations such as tirzepatide, sold as Mounjaro, followed and, in Dr. Pai's assessment, outperform semaglutide alone for weight loss specifically. A three-hormone GLP-1/GIP/glucagon combination is next in the pipeline. All three act on the brain to produce a gastric-paresis-like effect that suppresses appetite; injectable semaglutide is dosed weekly, starting at 0.25 mg and rising gradually to 2.4 mg, while an oral version, marketed as Rybelsus, must be taken daily.
Why the price collapsed in India
Mounjaro launched in the United States at roughly 1,000 dollars a month and earned its manufacturer, Eli Lilly, 8 billion dollars in its first year. The same drug reached India at about one-sixth of that price, 15,000 to 20,000 rupees a month, a decision Dr. Pai attributed to the sheer scale of global obesity rather than typical pricing behaviour from an American pharmaceutical company. With semaglutide's patent expiring and roughly eleven manufacturers preparing competing versions for the Indian market, he expects prices to fall further still.
Fitting the drug around a treatment cycle, not the other way round
Semaglutide and tirzepatide are not used during active attempts at conception. Dr. Pai's protocol is to bring weight down first, stop the drug, allow roughly a month for it to clear the system, then begin ovarian stimulation, retrieve and freeze embryos, and transfer around a month after that. He pointed to metformin as a precedent for changing clinical caution over time: once considered risky in pregnancy, it is now used throughout it, and he expects the same reassessment to happen with GLP-1 drugs as more data accumulates, citing an estimated 50,000 unplanned pregnancies among women taking semaglutide in the United States with no reported harm to those pregnancies.
This guide is based on a live Jivo Masterclass — Dr. Hrishikesh Pai taught doctors across Africa on February 15, 2026.
FROM THE LIVE Q&A
Dr. Ivan Ipavu (Uganda)
Why should we consider IVF over intrauterine insemination, and what are the complications of IVF?
Dr. Hrishikesh Pai
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.
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Frequently Asked Questions
What are the factors that reduce the success rate of IVF?▼
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.
Many women presenting with infertility have a white, cheese-like vaginal discharge. Could there be a connection?▼
This is usually a fungal infection, and both partners need treatment, along with lactobacillus supplements. Because a wet mount or culture can miss organisms such as Trichomonas, Chlamydia or Mycoplasma, Dr. Pai often gives combination therapy (an antifungal such as fluconazole plus an antibiotic such as azithromycin) with local clotrimazole cream, and screens for diabetes, since fungal infections are common in patients who are obese or diabetic.
A woman with blood group O negative delivered her first child and received anti-D prophylaxis, then had a miscarriage at 16 weeks. How should such couples be managed?▼
If antibody titres are very high, management becomes difficult. Where it is legally available, Dr. Pai suggested surrogacy carried by an Rh-negative surrogate as a way to avoid maternal antibody-mediated complications and repeated interventions such as cord blood transfusion, rather than risking complications like kernicterus in the baby.
Is letrozole considered more effective than clomiphene for ovulation stimulation?▼
Not universally. Dr. Pai calls clomiphene his master drug and reserves letrozole specifically for PCOS patients. His practice stratifies by AMH and antral follicle count: normal responders (AMH 2 to 3.5 ng/ml, AFC 7 to 15) receive clomiphene or clomiphene plus HMG; poor responders (AMH under 1.5, AFC under 7) also receive clomiphene plus HMG; hyper-responders with PCOS (AMH over 3.5, AFC over 15) receive letrozole; pure HMG is reserved for IVF cycles.
What is the referral process for sending a patient's case in for review?▼
Answered by the Jivo Healthcare coordination team rather than Dr. Pai directly: each referring doctor is assigned a relationship manager who collects and documents the case file, shares it with the Fortis coordinator and Dr. Pai's team, and returns a review with further guidance within 48 to 72 hours.
How do GLP-1 drugs like semaglutide produce weight loss?▼
They act on the brain to produce a gastric-paresis-like effect that suppresses appetite.
What is the difference between injectable and oral semaglutide?▼
Injectable semaglutide is dosed weekly, starting at 0.25 mg and rising gradually to 2.4 mg, while the oral version, marketed as Rybelsus, must be taken daily.
What third class of weight-loss drug is currently in development after GLP-1 and GLP-1/GIP combinations?▼
A three-hormone GLP-1/GIP/glucagon combination is next in the pipeline, following GLP-1 agonists such as semaglutide and GLP-1/GIP combinations such as tirzepatide.
In This Series: Diagnosis and Management of Infertile Couple - Latest Guidelines by WHO
- 1.Diagnosis and Management of the Infertile Couple
- 2.The WHO's 2025 Infertility Guideline: What Changed and Why It Matters
- 3.Diagnosing Infertility: The Female Workup, Step by Step
- 4.Male Factor Infertility: Semen Testing and Varicocele Treatment
- 5.PCOS and Ovulatory Dysfunction: Diagnosis Through Stepped Treatment
- 6.Weight-Loss Pharmacotherapy in Fertility Care: Semaglutide and Tirzepatide
- 7.Tubal Disease and Hydrosalpinx: Management and Ectopic Pregnancy Vigilance
- 8.Unexplained Infertility: From Expectant Management to IUI
- 9.Genital Tuberculosis: The Infertility Cause the WHO Guideline Misses
- 10.When to Move to IVF: Success Rates, Freezing and Genetic Testing
- 11.Fertility Preservation: Egg Freezing Before the Window Closes
- 12.Cross-Border Fertility Care: Treating Fibroids, Adenomyosis and Long-Distance Patients
- 13.The Next Frontier: AI-Driven ICSI and the Future of ART