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Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women.

ABSTRACT: Ovarian prostaglandins are critical in normal ovulation processes; thus, their inhibition may provide contraceptive benefits. This study was performed to determine the effect of the cyclooxygenase-2 (COX2) inhibitor celecoxib on ovulation and luteal events in women.The study had a randomized, double-blind, crossover design. Ovulatory, reproductive-aged women underwent ovarian ultrasound and serum hormone monitoring during four menstrual cycles (control cycle, treatment cycle 1, washout cycle, treatment cycle 2). Subjects received study drug (oral celecoxib 400 mg or placebo) either (a) once daily starting on cycle day 8 and continuing until follicle rupture or the onset of next menses if follicle rupture did not occur [pre-luteinizing hormone (LH) surge dosing] or (b) once daily beginning with the LH surge and continuing for 6 days (post-LH surge dosing). Subjects were randomly assigned to one of the above treatment schemes and received the other in the subsequent treatment cycle. The main outcomes were evidence of ovulatory and luteal dysfunction as determined by inhibited/delayed follicle rupture and reduced luteal progesterone synthesis or lifespan, respectively.A total of 20 women enrolled and completed the study (Group 1=10, Group 2=10), with similar demographics between groups. Nineteen subjects exhibited normal ovulation in the control cycle (one had a blunted LH peak). In comparison to control cycles, treatment cycles resulted in a significant increase in ovulatory dysfunction [pre-LH treatment: 30% (6/20), p=.04; post-LH treatment: 25% (5/20), p=.04]. Mean peak progesterone, estradiol, and LH levels and luteal phase length did not differ significantly between control and either treatment cycle.Although treatment with celecoxib before or after the LH surge increases the rate of ovulatory dysfunction, most women ovulate normally. Thus, this selective COX2 inhibitor appears to be of limited usefulness as a potential emergency contraceptive.

SUBMITTER: Edelman AB

PROVIDER: S-EPMC4040982 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women.

Edelman Alison B AB Jensen Jeffrey T JT Doom Carmen C Hennebold Jon D JD

Contraception 20120816 3

<h4>Background</h4>Ovarian prostaglandins are critical in normal ovulation processes; thus, their inhibition may provide contraceptive benefits. This study was performed to determine the effect of the cyclooxygenase-2 (COX2) inhibitor celecoxib on ovulation and luteal events in women.<h4>Study design</h4>The study had a randomized, double-blind, crossover design. Ovulatory, reproductive-aged women underwent ovarian ultrasound and serum hormone monitoring during four menstrual cycles (control cyc ...[more]

PMID: 22902348

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Project description:The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

Dataset Information

Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women.

Publications

Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women.

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