P-642 Low responders may benefit from undergoing ovarian stimulation with a long GnRH-agonist protocol with corifollitropin-alpha followed by hMG
Authors: Ferreira F.R , Sousa A.P , Cortesão P , Almeida-Santos T 
Published: June 2022

Study question

Can women with a suboptimal response benefit from undergoing ovarian stimulation with a long GnRH-agonist protocol with corifollitropin-alpha followed by hMG?

Summary answer

Women with a suboptimal response to ovarian stimulation may have better outcomes with a long GnRH-agonist protocol with corifollitropin-alpha and hMG.

What is known already

Low responders correspond to 9-24% of the women submitted to ovarian stimulation and represent one of the major challenges in assisted reproduction techniques. Currently, the evidence does not favor the short GnRH-antagonist or the long GnRH-agonist regimens for ovarian stimulation in poor ovarian responders. However, some studies have shown a higher number of retrieved oocytes with the long agonist protocol. Corifollitropin-alpha has been studied in both short and long ovarian stimulation regimens with promising results for poor responders, based on the lower cancellation rate and the higher number of retrieved oocytes and cryopreserved embryos.

Study design, size, duration

Retrospective cohort study. All women (n = 79) enrolled in an assisted reproductive treatment with a) suboptimal ovarian response, defined as &lt; 4 oocytes (subgroup A) or 4-9 oocytes (subgroup B) obtained after a short GnRH-antagonist protocol (SP) using rFSH/hMG and b) submitted to a second ovarian stimulation cycle with a long GnRH-agonist protocol using a single dose of triptorelin 3.75mg and corifollitropin-alpha followed by hMG - “simplified long protocol” (SLP), were included in the study.

Participants/materials, setting, methods

Demographic/clinic characteristics were recorded, including age, body mass index (BMI), anti-müllerian hormone (AMH), antral follicle count (AFC), cause of infertility, “Poseidon” classification, number of retrieved oocytes, mature oocytes, and embryos, pregnancy rate (per cycle) and live-birth rate (per embryo transfer). The outcomes of the second ovarian stimulation cycle (SLP) were compared with the outcomes of the first cycle (SP) in the same women/couple using the paired T-test/Wilcoxon for numerical and McNemar’s test for categorical data.

Main results and the role of chance

The age of women was 35.3±2.9 years old [29-40], the BMI was 23.7±4.1 kg/m2 [15.2-38.5], the AMH was 1.75±1.21 ng/mL [0.32-7.30] and the AFC was 9.5±3.7 [2-20]. The mean number of retrieved oocytes (8.46 versus 4.97, p&lt;0.001), mature oocytes (5.70 versus 2.93, p&lt;0.001), and embryos (1.21 versus 0.48, p&lt;0.001) were significantly higher with the SLP in comparison with the SP. The pregnancy (18.8% versus 5.1%, p = 0.008) and live-birth rates (28.9% versus 0%, p&lt;0.001) were significantly higher with the SLP. The cancellation rate was 3.8% and 7.6% in the SLP and SP, respectively (ns). There were 18 women (22.8%) in the subgroup A and 55 (69.6%) in the subgroup B. The other 6 cases (7.6%) correspond to cancellation cycles (absence of follicular response). Similar results were obtained in both subgroups, A and B, with a significantly higher numbers of retrieved oocytes, mature oocytes, and embryos. In the subgroup A, no clinical pregnancies were obtained with the SP while a2 cases occurred with the SLP (p&lt;0.001). One of those couples had a live birth (ns). The pregnancy (21.8% versus 7.4%, p = 0.033) and live-birth rates (31.0% versus 0, p=0.03) were significantly higher with the SLP in the subgroup B.

Limitations, reasons for caution

This was a cohort study with a relatively low number of patients. Future studies with a higher population size and a different design are needed to give robustness to our findings.

Wider implications of the findings

Women with a suboptimal response to ovarian stimulation with a short antagonist protocol may have a higher number of oocytes, higher number of mature oocytes and higher pregnancy and live-birth rates when undergoing treatment with a long GnRH-agonist protocol with corifollitropin-alpha and hMG.

Trial registration number

Not applicable