Oral Gonadotropin-Releasing Hormone Antagonists in the Treatment of Uterine Myomas: A Systematic Review and Network Meta-analysis of Efficacy Parameters and Adverse Effects.

OBJECTIVE: The aim of this systematic review is to gather and synthesize evidence regarding the use of oral gonadotrophin-releasing hormone (GnRH) antagonist for the treatment of bleeding associated with uterine myomas. DATA SOURCES: Web of Science, and MEDLINE databases were searched electronically on March 5, 2021, using combinations of the relevant Medical Subject Headings terms and keywords. The search was restricted to the English language and to human studies. METHODS OF STUDY SELECTION: Only randomized controlled trials involving patients with heavy menstrual bleeding associated with uterine myomas treated with different doses of oral nonpeptide GnRH antagonists with or without add-back therapy were included. Studies comparing oral nonpeptide GnRH antagonists with treatments other than placebo were also excluded. TABULATION, INTEGRATION, AND RESULTS: A total of 5 randomized trials including 2463 women were included in the analyses. Included studies were found to be at low risk of bias. When treatments were compared against placebo, the top 3 treatments for bleeding suppression were elagolix 600 mg, 400 mg, and 200 mg without add-back. Elagolix 600 mg without add-back therapy had a significantly higher risk of amenorrhea than lower doses of elagolix with and without add-back and relugolix as well. Uterine volume changes were more pronounced in therapies without add-back. All treatments were associated with significantly improved quality of life scores, both for myoma symptom-related and overall health-related scores. With the exception of relugolix with high-dose add-back, all treatments significantly increased low-density lipoprotein (LDL) levels. Again, all treatment modalities except for elagolix 200 mg without add-back significantly increased LDL-to-HDL ratio. The increase was highest for treatment without add-back therapy. CONCLUSION: Oral GnRH antagonists seem to be effective for myoma-associated bleeding and for improving quality of life. The safety profile is acceptable for short-term use, but lipid metabolism is affected.

Assisted reproductive technology for women with endometriosis, a clinically oriented review.

PURPOSE OF REVIEW: To discuss optimal management of an assisted reproductive technology (ART) cycle in women with endometriosis. RECENT FINDINGS: New studies involving euploid embryo transfers provide more insight on the etiology of endometriosis-associated infertility. Oocyte competence to reach live birth seems unlikely to be affected by the disease. Routine medical or surgical treatment prior to an ART cycle does not appear beneficial. Short gonadotropin releasing hormone (GnRH) antagonist or progestin primed ovarian stimulation protocols seem to be proper first choices, depending on the intention for a fresh embryo transfer. Low-quality evidence supports frozen thawed over fresh embryo transfer. Ovarian stimulation for ART does not seem to be associated with symptom progression or recurrence. SUMMARY: How endometriosis affects fertility is still unclear, but ART is an effective pragmatic treatment. Each woman with endometriosis must be assessed with a holistic approach, and in the absence of an indication for otherwise, ART cycles can be kept simple with patient-friendly protocols. Whether a frozen embryo transfer is better than a fresh one should be investigated.

Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis.

IMPORTANCE: Preimplantation genetic testing for aneuploidy (PGT-A) to deselect aneuploid embryos in assisted reproductive technology (ART) treatment cycles may hold promise by augmenting pregnancy rates per transfer and reducing pregnancy loss rates for patients with unexplained recurrent pregnancy loss (RPL). OBJECTIVE: To explore effectiveness of PGT-A in managing unexplained RPL by evaluating several key aspects: the likelihood of live birth in a subsequent spontaneous pregnancy, whether women with unexplained RPL have a higher rate of aneuploidy, whether euploid blastocysts offer comparable live birth rate (LBR) in patients with unexplained RPL, whether the endometrium is less selective in unexplained RPL loss, and whether PGT-A increases the LBR or reduces pregnancy losses until delivery. DATA SOURCES: PubMed and Cochrane Library databases were searched from inception until June 2024. STUDY SELECTION AND SYNTHESIS: Studies involving patients with ≥2 unexplained RPL who underwent ART with or without PGT-A or expectant management were included. MAIN OUTCOME MEASURES: The primary outcome measure was the LBR. Secondary outcome measures were aneuploidy rate, clinical pregnancy rate, and clinical pregnancy loss rate. RESULTS: Whether couples with unexplained RPL have higher embryo aneuploidy rates remains equivocal. Euploid blastocyst transfers yielded comparable clinical pregnancy loss rate (odds ratio [OR], 1.10; 95% confidence interval [CI], 0.57-2.13) and LBR (OR, 1.04; 95% CI, 0.74-1.44) in patients with and without unexplained RPL. Comprehensive chromosome analysis of products of conception shows similar aneuploidy rates between patients with and without RPL and does not support the less selective endometrium hypothesis. Preimplantation genetic testing for aneuploidy decreased clinical pregnancy loss rate (OR, 0.42; 95% CI, 0.27-0.67) and enhanced LBR per transfer (OR, 2.17; 95% CI, 1.77-2.65) and LBR per patient (OR, 1.85; 95% CI, 1.18-2.91) in patients with unexplained RPL. CONCLUSION AND RELEVANCE: Current low-quality evidence suggests that PGT-A enhances LBR per transfer and per patient in unexplained RPL. Well-designed randomized controlled trials comparing ART with PGT-A vs. expectant management for unexplained RPL are warranted. CLINICAL TRIAL REGISTRATION NUMBER: CRD42021291546.