Abnormal luteal function is a common issue in assisted reproduction techniques associated with ovarian stimulation probably due to low levels of LH in the middle and in the late luteal phase. This defect seems to be associated with supraphysiological steroid levels at the end of follicular phase. The luteal phase insufficiency has not got a diagnostic test which has proven reliable in a clinical setting. Luteal phase after ovarian stimulation becomes shorter and insufficient, resulting in lower pregnancy rates. Luteal phase support with progesterone or hCG improves pregnancy outcomes and no differences are found among different routes of administration. However, hCG increases the risk of ovarian hyperstimulation syndrome. In relation to the length of luteal support, the day of starting it remains controversial and it does not seem necessary to continue once a pregnancy has been established. After GnRHa triggering ovulation, intensive luteal support or hCG bolus can overcome the defect in luteal phase, but more studies are needed to show the LH utility as support.
PURPOSE Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824 ), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1–positive populations (alpha .025 for each population). RESULTS Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1–positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1–positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1–positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.
LH is a glycoprotein that plays a crucial role in folliculogenesis during the natural ovarian cycles. It has the same activity and shares receptors with hCG. However the use of LH in combination with FSH in controlled ovarian stimulation remains controversial. A practical approach concerning the usefulness of LH according to the endogenous level of LH is described herein. Specific groups of patients can benefit from ovarian stimulation with LH. New applications of LH/hCG activity are also discussed.
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