Recombinant follicular stimulating hormone plus recombinant luteinizing hormone versus human menopausal gonadotropins- does the source of LH bioactivity affect ovarian stimulation outcome?

OBJECTIVE: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) activate distinct intracellular signaling cascades. However, due to their similar structure and common receptor, they are used interchangeably during ovarian stimulation (OS). This study aims to assess if the source of LH used during OS affects IVF outcome. PATIENTS AND METHODS: This was a cross sectional study of patients who underwent two consecutive IVF cycles, one included recombinant follicular stimulating hormone (FSH) plus recombinant LH [rFSH+rLH, (Pergoveris)] and the other included urinary hCG [highly purified hMG (HP-hMG), (Menopur)]. The OS protocol, except of the LH preparation, was identical in the two IVF cycles. RESULTS: The rate of mature oocytes was not different between the treatment cycles (0.9 in the rFSH+rLH vs 0.8 in the HP-hMG, p = 0.07). Nonetheless, the mean number of mature oocytes retrieved in the rFSH+rLH treatment cycles was higher compared to the HP-hMG treatment cycles (10 ± 5.8 vs 8.3 ± 4.6, respectively, P = 0.01). Likewise, the mean number of fertilized oocytes was higher in the rFSH+rLH cycles compared with the HP-hMG cycles (8.5 ± 5.9 vs 6.4 ± 3.6, respectively, p = 0.05). There was no difference between the treatment cycles regarding the number of top-quality embryos, the ratio of top-quality embryos per number of oocytes retrieved or fertilized oocytes or the pregnancy rate. CONCLUSION: The differences in treatment outcome, derived by different LH preparations reflect the distinct physiological role of these molecules. Our findings may assist in tailoring a specific gonadotropin regimen when assembling an OS protocol.

GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study.

STUDY QUESTION: Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone? SUMMARY ANSWER: Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone. WHAT IS KNOWN ALREADY: hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates. STUDY DESIGN, SIZE, DURATION: A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m2 versus 23.7 kg/m2) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43-1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR= 1.98 (1.05-3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group. LIMITATIONS, REASONS FOR CAUTION: None. WIDER IMPLICATIONS OF THE FINDINGS: The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by TRIO Fertility. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02703584. DATE OF TRIAL REGISTRATION: March 2016. DATE OF FIRST PATIENT'S ENROLLMENT: May 2016.