Impact of clomiphene citrate during ovarian stimulation on the luteal phase after GnRH agonist trigger.
The use of a gonadotrophin-releasing hormone (GnRH) agonist to trigger final oocyte maturation in a GnRH antagonist protocol has been associated with poorer clinical outcomes due to an increased luteal-phase defect. It has been shown that LH activity is crucial in a normal luteal phase. Studies assessing the LH concentrations after clomiphene citrate co-treatment have observed increased luteal-phase LH concentrations. The purpose of this prospective cohort study was to analyse the effect of clomiphene citrate on the endocrine profile in the luteal phase when using GnRH agonist trigger. This was evaluated in eight oocyte donors undergoing ovarian stimulation using clomiphene citrate in combination with recombinant FSH compared with a control group of five donors treated with recombinant FSH only. The endocrine profile was comparable in both groups, except for serum LH concentrations on the day after trigger (121.3±53.0IU/l versus 52.9±21.5IU/l, respectively, P=0.022). No significant differences in LH concentrations were found on the day of trigger or 5days after oocyte retrieval. In conclusion, a luteal-phase defect was observed despite treatment with clomiphene citrate during ovarian stimulation. The use of gonadotrophin-releasing hormone (GnRH) agonist to trigger ovulation in IVF has been associated with poorer pregnancy outcomes due to an increased luteal-phase defect. The luteal phase is the last phase of the menstrual cycle and is defined as the period between ovulation and the beginning of pregnancy or menses. It has been shown the activity of LH is crucial in a normal luteal phase. Studies assessing the LH concentrations after clomiphene citrate, an oestrogen receptor inhibitor, co-treatment have observed increased luteal-phase LH concentrations. The purpose of this prospective cohort study was to analyse the effect of clomiphene citrate on menstrual cycle day 2-6 on the hormone profile in the luteal phase when using GnRH agonist trigger. This was evaluated was in eight oocyte donors undergoing ovarian stimulation using recombinant FSH compared with a control cohort of donors treated with recombinant FSH only. The current prospective cohort study reports higher LH concentrations on the day after GnRH agonist trigger, but not 5days after oocyte retrieval (i.e. in the luteal phase). In conclusion, a luteal-phase defect was observed despite the administration of clomiphene citrate during ovarian stimulation. Additional treatment with clomiphene citrate in the follicular phase is therefore not a valid alternative to prevent luteal-phase defect after GnRH agonist trigger.
Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
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Derksen
Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
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Tournaye
Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
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Stoop
Reproductive Immunology and Implantation, Vrije Universiteit Brussel, Brussels, Belgium.
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Van Vaerenbergh
Reproductive Immunology and Implantation, Vrije Universiteit Brussel, Brussels, Belgium.
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Bourgain
Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
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Polyzos
Centre for Outcomes Research and Laboratory for Experimental Surgery, UZ Brussel, Brussels, Belgium.
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Haentjens
Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: christophe.blockeel@uzbrussel.be.
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Blockeel
D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D004717:Endometrium / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D010062:Ovulation Induction / Q000379:methods*; D011374:Progesterone / Q000097:blood
D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
GnRH agonist trigger; GnRH antagonist; IVF/ICSI; clomiphene citrate; ovarian stimulation; recombinant FSH