Predicting suboptimal oocyte yield following GnRH agonist trigger by measuring serum LH at the start of ovarian stimulation

Abstract

STUDY QUESTION Are the LH levels at the start of ovarian stimulation predictive of suboptimal oocyte yield from GnRH agonist triggering in GnRH antagonist down-regulated cycles? SUMMARY ANSWER LH levels at the start of ovarian stimulation are an independent predictor of suboptimal oocyte yield following a GnRH agonist trigger. WHAT IS KNOWN ALREADY A GnRH agonist ovulation trigger may result in an inadequate oocyte yield in a small subset of patients. This failure can range from empty follicle syndrome to the retrieval of much fewer oocytes than expected. Suboptimal response to a GnRH agonist trigger has been defined as the presence of circulating LH levels <15 IU/l 12 h after triggering. It has been shown that patients with immeasurable LH levels on trigger day have an up to 25% risk of suboptimal response. STUDY DESIGN, SIZE, DURATION In this retrospective cohort study, all patients (n = 3334) who received GnRH agonist triggering (using Triptoreline 0.2 mg) for final oocyte maturation undergoing a GnRH antagonist cycle in our centre from 2011 to 2017 were included. The primary outcome of the study was oocyte yield, defined as the ratio between the total number of collected oocytes and the number of follicles with a mean diameter >10 mm prior to GnRH agonist trigger. PARTICIPANTS/MATERIALS, SETTING, METHODS The endocrine profile of all patients was studied at initiation as well as at the end of ovarian stimulation. In order to evaluate whether LH levels, not only at the end but also at the start, of ovarian stimulation predicted oocyte yield, we performed multivariable regression analysis adjusting for the following confounding factors: female age, body mass index, oral contraceptives before treatment, basal and trigger day estradiol levels, starting FSH levels, use of highly purified human menopausal gonadotrophin and total gonadotropin dose. Suboptimal response to GnRH agonist trigger was defined as <10th percentile of oocyte yield. MAIN RESULTS AND THE ROLE OF CHANCE The average age was 31.9 years, and the mean oocyte yield was 89%. The suboptimal response to GnRH agonist trigger cut-off (<10th percentile) was 45%, which was exhibited by 340 patients. Following confounder adjustment, multivariable regression analysis showed that LH levels at the initiation of ovarian stimulation remained an independent predictor of suboptimal response even in the multivariable model (adjusted OR 0.920, 95% CI 0.871–0.971). Patients with immeasurable LH levels at the start of stimulation (<0.1 IU/l) had a 45.2% risk of suboptimal response, while the risk decreased with increasing basal LH levels; baseline circulating LH <0.5 IU/L, <2 IU/L and <5 IU/L were associated with a 39.1%, 25.2% and 13.6% risk, respectively. LIMITATIONS, REASONS FOR CAUTION The main limitation of the study is its retrospective design. WIDER IMPLICATIONS OF THE FINDINGS This is the largest study of GnRH agonist trigger cycles only, since most of the previous research on the predictive value of basal LH levels was performed in dual trigger cycles. LH values should be measured prior to start of ovarian stimulation. In cases where they are immeasurable, suboptimal response to GnRH agonist trigger can be anticipated, and an individualized approach is warranted. STUDY FUNDING/COMPETING INTEREST(S) There was no funding and no competing interests. TRIAL REGISTRATION NUMBER Not applicable.

Ovarian follicular function is not altered by SARS–CoV-2 infection or BNT162b2 mRNA COVID-19 vaccination

“…This ratio represents the ability of the granulosa cells to secrete enzymes that release the cumulus oocyte complex from the wall of the follicle in response to the LH surge, thereby allowing its aspiration. An oocyte yield of 45% or less was defined as sub-optimal ( Popovic-Todorovic et al , 2019 ).…”

Endocrine Requirements for Oocyte Maturation Following hCG, GnRH Agonist, and Kisspeptin During IVF Treatment

“…Indeed, the risk of encountering an LH <15 iU/L at 12 h following GnRHa (a threshold commonly used to denote a suboptimal LH rise), occurred in 17.3% of those with a pre-trigger LH <0.5 iU/L but only 3.8% if pre-trigger LH was >2 iU/L. Thus, adjusting the timing and dose of the GnRH antagonist to avoid excessive suppression could further optimize the efficacy of the trigger ( 30 ).…”

Gonadotropin levels at the start of ovarian stimulation predict normal fertilization after hCG re‐trigger in GnRH antagonist cycles

“…It can be therefore said that low FSH and LH levels at the start of COS are not direct causes of infertility but may be incidental symptoms. There have been many reports regarding suboptimal oocyte yield after GnRHa trigger 43 ; however, most of the reports describe the possible association of hormone levels with oocyte yield after re‐trigger, but not with fertilization or embryo development. Further investigation will be necessary focusing on the association of hormone levels with fertilization, embryo development, pregnancy, and delivery after re‐trigger.…”