With traditional in vitro fertilization (IVF), complex ovarian stimulation regimens and multiple clinic visits and procedures are typical. As a result, the treatment comes with a price tag that is out of reach for many individuals. A minimal stimulation IVF procedure, now available at Cleveland Clinic, offers lower costs and good success rates for appropriately selected patients.
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Minimal stimulation IVF
“With minimal stimulation IVF, we typically administer clomiphene citrate and low-dose gonadotropins,” says Laura Detti, MD, Chair of the Department of Subspecialty Care for Women’s Health. “The technique is the same but the number of oocytes harvested is less than with conventional IVF.”
A typical “mini-IVF” stimulation protocol is 50–100 mg/day orally of clomiphene citrate from cycle Day 3 until the day before triggering, plus injections of 75–150 IU of human menopausal gonadotropin on cycle Days 4–7. The exact dosage depends on a patient’s ovarian reserve status and body mass index.
Costs for the mini-IVF procedure are not as high because less medication is used, fewer office visits and ultrasounds are needed, and fewer oocytes are retrieved. The overall success rate is somewhat lower than with traditional IVF, but not in all patients.
Lower doses of gonadotrophin increases oocyte quality
“The literature shows that in women with decreased ovarian reserve, administering lower doses of gonadotrophin results in increased oocyte quality,” she says. “The mini protocol is advantageous in those cases because we can do multiple IVF cycles and produce high-quality embryos that are more likely to result in a pregnancy.”
Guidelines from the American Society for Reproductive Medicine (ASRM) indicate that “strong consideration” should be given to using mild ovarian stimulation in patients pursuing IVF who are poor responders. Advanced maternal age, previous poor response and abnormal ovarian reserve tests are the three tests for likelihood of poor response that make up the well-known Bologna criteria.
In poor responders, according to ASRM, there is “fair” evidence that clinical pregnancy rates after IVF are not substantially different with use of low-dose versus conventional-dose gonadotropins for IVF. No data exist, however, about live-birth rates with mini-IVF.
Dr. Detti believes that an IVF protocol with lower-dose stimulation also is appropriate for women with tubal factor infertility who are under 35. “Age is a factor in success of IVF, so younger patients perform better.”
Besides costs, other factors to be considered when weighing a choice between traditional and mini IVF are potential treatment complications, such as ovarian hyperstimulation syndrome. Preliminary reports in the literature, which must be interpreted cautiously, suggest an inverse relationship between the extent of ovarian stimulation and pregnancy complications and perinatal outcomes.
Although mini IVF is not new, few centers offer it, according to Dr. Detti. “High-volume IVF centers typically don’t have an interest in minimal stimulation because they don’t need the extra volume and the procedure would not be cost-effective for them.”
In contrast, she says, the Cleveland Clinic philosophy is focused on helping patients who meet the criteria for minimal stimulation IVF get access to the lower-cost option, particularly during the era of COVID-19. It has already been used successfully by the institution in selected patients, and plans are in the works to make it available on a larger scale.
“In the past, we’ve offered minimal stimulation on request, but we want to make more physicians and patients aware of it at this point,” says Dr. Detti. “It’s an affordable way to achieve a pregnancy and we welcome referrals of women who meet the criteria and might benefit.”