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DENVER -- Two common treatments for advanced stage endometriosis were associated with negative reproductive outcomes for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared to no treatment, an interim analysis of a randomized three-arm clinical trial showed.

Women with endometriosis randomized to dienogest (Visanne) -- a fourth-generation progestin -- had lower birth rates per single embryo transfer than those in the control group who had no treatment prior to IVF/ICSI (17.4% vs 38.2%, P=0.042), reported Johnny Awwad, MD, executive chair of women's services and division chief of reproductive medicine at Sidra Medicine in Doha, Qatar, during a presentation at the American Society for Reproductive Medicine annual meeting.

Outcomes with dienogest were similar to those among women randomized to triptorelin (Trelstar), a gonadotropin-releasing hormone (GnRH) agonist (18.1%). Additionally, more chemical miscarriages occurred in the dienogest and triptorelin groups compared to the control group, which was clinically relevant but not statistically significant, Awwad said.

Past research has questioned whether GnRH agonists improve IVF outcomes, Awwad said, and there's interest in exploring how other compounds could improve pregnancy outcomes for patients with endometriosis-associated infertility. For instance, a systematic review found that dienogest treatment was comparable to GnRH agonists for alleviating pain in endometriosis patients.

In this study, however, the control group had higher implantation rates, live birth rates per single embryo transfer, and live birth rate per initiated cycle than dienogest or triptorelin. Awwad concluded that the potentially detrimental effect of dienogest in particular on IVF outcomes indicated by this study warrants further investigation.

Sangita Jindal, PhD, of Montefiore Institute for Reproductive Medicine and Health in Hartsdale, New York, who moderated the session, told MedPage Today that it was "a well-designed study" but she didn't know "if it's powered sufficiently to conclude that these progestins are harming patients' chances." She noted that the study's statistician "will tell them at some point whether these findings are significant and they can make generalizable conclusions from the number of patients in each arm instead of going further, but I suspect ... that they will probably discontinue this."

Rachel Weinerman, MD, an ob/gyn and reproductive endocrinologist at Case Western Reserve University in Cleveland who wasn't involved in the study, explained that "endometriosis lesions get smaller or atrophy in response to high-dose progestin, so it's understandable to think that giving a progestin before a patient gets pregnant could be helpful in women with endometriosis." But this study, she said, "demonstrates that there was no improvement in live birth and possibly a decrease in live birth with progestin treatment prior to IVF."

Weinerman added that because the study was small, the results should be interpreted cautiously, though "it does provide some evidence that even though treatment with a progestin prior to IVF sounds like a good idea, it is probably not beneficial and may be harmful."

For this randomized controlled open-label clinical trial, researchers assessed the impact of prolonged dienogest and GnRH agonist administration on live birth rates in women with advanced-stage endometriosis undergoing IVF/ICSI compared to no pre-treatment. Eighty-six women with stage III-IV endometriosis were randomized to three groups: Group A (n=29) received dienogest (2 mg orally daily) and Group B (n=29) received the GnRH agonist triptorelin (3.75 mg intramuscularly monthly), each for 3 consecutive months, while in Group C (n=28) women received no prior treatment, which served as the control.

Participants were premenopausal, from ages 18 through 38 years, had a BMI between 18 and 32, were planning IVF or ICSI fertility treatment, and were diagnosed with ovarian endometriosis that was confirmed radiologically by ultrasound or MRI. They had normal uterine cavity and normal hormonal profiles. Exclusion criteria included preexisting medical conditions, risk for thromboembolic events, male azoospermia, and a history of three or more miscarriages.

In total, 70 women underwent a fresh embryo transfer. Cycle cancellations because of no oocytes or lack of embryos were fairly equal across groups. Patient and cycle characteristics were also similar across groups and there were no differences in the number of oocytes and 2PN zygotes, or in the maturation, fertilization, cleavage, and blastulation rates.

Awwad noted that the primary limitation of this interim analysis is the low statistical power and small sample size, which limits generalizability.

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