The LH endocrine profile in gonadotropin-releasing hormone analogue cycles.

Research question: What does the evolution of serum luteinizing hormone (LH) levels look like throughout the follicular phase of cycles in which gonadotrophins and gonadotropin-releasing hormone (GnRH) analogues in the context of ovarian stimulation for assisted reproduction technologies (ART) were used?Design: This was a retrospective, observational cohort study in a tertiary infertility clinic. 1303 patients aged between 18 and 43 years of age were included with a total of 2200 cycles for ART, using GnRH-analogues for pituitary down-regulation stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH). Follicular evolution of LH during ovarian stimulation in different treatment protocols was modeled as repeated measures.Results: LH evolution showed a significant decrease in antagonist/hMG cycles of 0.17 IU/L per day (95% CI [-0.20, -0.12]) and 0.26 IU/L per day in rec-FSH cycles (95% CI [-0.29, -0.22]). This decrease was significantly stronger in rec-FSH cycles than in hMG cycles (estimated difference of 0.09 IU/L per day, 95% CI [0.04, 0.15]). Short agonist/hMG cycles showed a significant increase in LH of 0.04 IU/L per day (95% CI [0.01, 0.08]), while the increase of 0.01 IU/L per day in cycles with rec-FSH was not significant (95% CI [-0.08, 0.10]).Conclusion: Follicular evolution of LH during controlled ovarian stimulation differs between different GnRH analogue cycles. A statistically significant decrease in LH was shown in GnRH antagonist cycles being more pronounced with rec-FSH compared to hMG. This decrease in LH in antagonist cycles and the potential impact on estradiol levels and follicle growth needs further examination.

Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, parallel-group pragmatic trial in infertile women with at least one patent tube at hysterosalpingo-foam sonography (HYFOIL study).

INTRODUCTION: Tubal patency testing is an essential part in the fertility workup of many subfertile women. Hysterosalpingography (HSG) has long been the test of choice in many clinics. There is evidence from a large randomised multicentre trial and from a recent meta-analysis that women who had HSG using oil soluble contrast medium (OSCM) had higher rates of ongoing pregnancy compared with women who underwent this procedure using water contrast. However, the field is moving away from HSG and nowadays hysterosalpingo-foam sonography (Hyfosy) using ultrasound guidance is considered as the first line office tubal patency test. Therefore, a large multicentre randomised clinical trial (RCT) will be initiated to evaluate if flushing the fallopian tubes with OSCM after a normal Hyfosy showing at least one patent fallopian tube will increase the live birth rate as compared with no flushing. METHODS AND ANALYSIS: We plan a multicentre two arm, 1:1 randomised, open-label pragmatic comparative trial in 12 Belgian centres. After informed consent, we will randomise infertile women between 18 and 40 years of age, undergoing Hyfosy as part of the fertility workup to Hyfosy with additional tubal flushing with OSCM versus Hyfosy without additional flushing. Infertility is defined as lack of conception despite 12 months of unprotected intercourse, or three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy, all three in combination with at least one patent tube on Hyfosy. Primary endpoint will be live birth with conception within 6 months after randomisation. ETHICS AND DISSEMINATION: Approval on 11 May 2021 by the Ethics Committee from ZNA Hospital Antwerp who was the central Ethics Committee for the Clinical Trial Regulation Pilot (Pilot 412) in the 12 centres. The findings from this RCT will be disseminated in peer-reviewed publications and presentations at scientific international meetings. TRIAL REGISTRATION NUMBERS: EudraCT number: 2020-002135-30 and NCT04379973.