Director, Fortis Bloom IVF Centre, Fortis Bloom IVF Centre
Part 8 of 13 in Diagnosis and Management of Infertile Couple - Latest Guidelines by WHO
Unexplained Infertility: From Expectant Management to IUI
August 28, 2026
In the majority of Dr. Pai's patients, every individual test comes back normal: ovulation is occurring, the tubes are patent, the uterine cavity is unremarkable, and semen parameters sit within WHO's reference ranges. That combination defines unexplained infertility, failure to conceive after 12 months of regular, unprotected intercourse despite a normal workup on both partners.
Two steps before IUI, not one
WHO suggests expectant management, rather than unstimulated IUI cycles, as the first step for couples with unexplained infertility. In Dr. Pai's practice that means clomiphene combined with timed intercourse around ovulation for 3 to 6 months. Where that fails, WHO's next recommendation is stimulated IUI cycles, which is where most of his own patients begin, since expectant management alone is a harder sell to couples who have already been trying to conceive.
The regimen and the numbers behind it
A typical stimulated cycle uses clomiphene 50 mg twice daily from day 2 to day 6, plus HMG 150 IU on days 7 and 9, with a trigger injection of hCG once the leading follicle reaches 18 to 20 millimetres on scan, followed by insemination with washed, prepared sperm. Dr. Pai runs 2 to 3 cycles as standard, though up to 6 is reasonable if a couple wants to continue, and estimated an overall success rate of around 30 percent. He described IUI as the treatment with the most potential to be delivered locally in Africa rather than requiring travel to India: a functioning IUI lab costs roughly 1,000 to 2,000 dollars to set up, and roughly 80 percent of infertile couples, in his estimate, can be helped without ever needing IVF, provided laparoscopy, hysteroscopy, ultrasound and a competent IUI programme are all in place.
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. Edgar Mumba
Many women presenting with infertility have a white, cheese-like vaginal discharge. Could there be a connection?
Dr. Hrishikesh Pai
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.
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Frequently Asked Questions
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.
Can you say more about the injectable medications you mentioned for weight loss and obesity management?▼
Three drug classes now exist: GLP-1 agonists (semaglutide), GLP-1/GIP combinations (tirzepatide, marketed as Mounjaro), and a GLP-1/GIP/glucagon combination about to be released. Injectable semaglutide starts at 0.25 mg subcutaneously, rising gradually to 2.4 mg; an oral form (Rybelsus) is also available but must be taken daily rather than weekly. Mounjaro, launched in the US two years earlier at roughly $1,000 a month, was released in India at about one-sixth of that cost (roughly Rs 15,000 to 20,000 a month) because of the scale of global obesity; with semaglutide's patent expiring in March and around eleven companies preparing to launch competing versions in India by April, prices are expected to fall further.
There is a lot of misinformation online about Ozempic and similar drugs. What class of drug is this, and how real are the risks?▼
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.
What defines unexplained infertility?▼
It is failure to conceive after 12 months of regular, unprotected intercourse despite a normal workup on both partners: ovulation is occurring, the tubes are patent, the uterine cavity is unremarkable, and semen parameters sit within WHO's reference ranges.
What is the first step WHO recommends before starting IUI for unexplained infertility?▼
WHO suggests expectant management before unstimulated IUI cycles, meaning clomiphene combined with timed intercourse around ovulation for 3 to 6 months before moving to stimulated IUI.
How many IUI cycles are typically recommended, and what is the average success rate?▼
2 to 3 cycles are standard, though up to 6 is reasonable if a couple wants to continue, with an overall estimated success rate of around 30 percent.
How much does it cost to set up a functioning IUI lab?▼
A functioning IUI lab costs roughly 1,000 to 2,000 dollars to set up, and roughly 80 percent of infertile couples can be helped without ever needing IVF, provided laparoscopy, hysteroscopy, ultrasound and a competent IUI programme are all in place.
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