Early and short follicular gonadotropin-releasing hormone antagonist supplementation improves the meiotic status and competence of retrieved oocytes in in vitro fertilization-embryo transfer cycles

Johnny S. Younis, Sofia Soltsman, Ido Izhaki, Orit Radin, Shalom Bar-Ami, Moshe Ben-Ami

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Objective: To investigate whether early and short follicular administration of GnRH antagonist using the flexible protocol has the potential to improve IVF-ET clinical results. Design: Prospective, controlled, randomized study. Setting: University-affiliated assisted reproductive technology unit. Patient(s): Fifty-three consecutive infertile women were enrolled to the study and control groups. Intervention(s): Both groups were treated with recombinant FSH and the flexible GnRH antagonist protocol. Women in the study group were additionally supplemented with three injections of GnRH antagonist (0.25 mg/d on days 1, 2, and 3 of the menstrual cycle). Main Outcome Measure(s): Hormonal milieu, oocyte meiotic status, competence for normal fertilization, cleavage, and clinical pregnancy rate. Result(s): Both groups had comparable baseline characteristics. The duration of recombinant FSH treatment was significantly longer in the study group as compared with the control group (10.9 ± 3.1 and 9.7 ± 1.3 days, respectively). The number of follicles ≥14 mm and E2 level on the day of hCG administration, number of retrieved oocytes, and endometrial thickness were similar between the two groups. However, the fertilization rate was significantly higher in the study as compared with the control group (85% ± 16% and 69% ± 24%, respectively). Moreover, the cumulative rate of mature first polar body oocytes was significantly higher in the study group as compared with the control group (93% and 85%, respectively). Concomitantly, day-3 FSH and LH levels after initiation of treatment were significantly lower in the study as compared with the control group (6.1 ± 2.4 mIU/mL vs. 7.2 ± 1.9 mIU/mL and 2.4 ± 1.6 mIU/mL vs. 5.6 ± 2.7 mIU/mL, respectively). Conclusion(s): Early and short follicular GnRH antagonist supplementation using flexible GnRH antagonist treatment improves the meiotic status and competence of retrieved oocytes. It seems that early and short pituitary shutdown has the potential to improve clinical results in IVF-ET GnRH antagonist cycles.

Original languageEnglish
Pages (from-to)1350-1355
Number of pages6
JournalFertility and Sterility
Volume94
Issue number4
DOIs
StatePublished - Sep 2010
Externally publishedYes

Bibliographical note

Funding Information:
We prospectively recruited 53 consecutive infertile women referred to our center for intracytoplasmic sperm injection (ICSI) owing to male factor infertility. Regularly menstruating women with two intact ovaries, age <39 years, body mass index 18–32 kg/m 2 , and normal uterine cavity determined by hysterosalpingography and/or hysteroscopy were included. Exclusion criteria were polycystic ovary syndrome (according to the 2003 Rotterdam Consensus Criteria) (11, 12) , severe endometriosis, low ovarian reserve, thyroid disease, diabetes mellitus, significant hyperprolactinemia, and hypogonadotropic hypogonadism. Women in the study could participate in the study only once. All women participating in the study were recruited after failure to achieve pregnancy using the long/short GnRH agonist protocol. Women with more than four previous unsuccessful ART attempts of treatment were excluded. Our study was registered at ClinicalTrials.gov , a service of the U.S. National Institutes of Health, in accordance with good clinical practice guidelines. The ClinicalTrials.gov identifier is NCT00461422. The study was performed in a prospective, randomized, controlled manner in a university-affiliated reproductive medicine unit. Biologists in the IVF and endocrine laboratories, as well as ultrasound technicians, were blinded to the drug regimen. Randomization between the study and control groups was performed using a computer-generated list before initiation of stimulation. The research project was approved by the Poriya Medical Center Institutional Review Board, and an informed consent form was signed by each woman participating in the study.

Funding

We prospectively recruited 53 consecutive infertile women referred to our center for intracytoplasmic sperm injection (ICSI) owing to male factor infertility. Regularly menstruating women with two intact ovaries, age <39 years, body mass index 18–32 kg/m 2 , and normal uterine cavity determined by hysterosalpingography and/or hysteroscopy were included. Exclusion criteria were polycystic ovary syndrome (according to the 2003 Rotterdam Consensus Criteria) (11, 12) , severe endometriosis, low ovarian reserve, thyroid disease, diabetes mellitus, significant hyperprolactinemia, and hypogonadotropic hypogonadism. Women in the study could participate in the study only once. All women participating in the study were recruited after failure to achieve pregnancy using the long/short GnRH agonist protocol. Women with more than four previous unsuccessful ART attempts of treatment were excluded. Our study was registered at ClinicalTrials.gov , a service of the U.S. National Institutes of Health, in accordance with good clinical practice guidelines. The ClinicalTrials.gov identifier is NCT00461422. The study was performed in a prospective, randomized, controlled manner in a university-affiliated reproductive medicine unit. Biologists in the IVF and endocrine laboratories, as well as ultrasound technicians, were blinded to the drug regimen. Randomization between the study and control groups was performed using a computer-generated list before initiation of stimulation. The research project was approved by the Poriya Medical Center Institutional Review Board, and an informed consent form was signed by each woman participating in the study.

FundersFunder number
Poriya Medical Center
Foundation for the National Institutes of Health

    Keywords

    • GnRH antagonist
    • follicular recruitment
    • oocyte competence
    • oocyte meiotic status

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