Dataset Information

Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.

ABSTRACT:

Background

Recent studies have indicated the use of gonadotropin-releasing hormone antagonists (GnRH-ant) as an adjuvant treatment to prevent premature luteinization (PL) and improve the clinical outcomes in patients undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI). However, the results of these studies are conflicting.

Methods

We conducted a systematic review and meta-analysis of randomized trials aiming to compare the clinical efficacy of GnRH-ant in COS/IUI cycles. Twelve studies were identified that met inclusion criteria and comprised 2,577 cycles assigned to COS/IUI combined GnRH-ant or COS/IUI alone.

Results

Meta-analysis results suggested that GnRH-ant can significantly increase the clinical pregnancy rate (CPR) (OR?=?1.42; 95% CI, 1.13-1.78) and decrease the PL rate (OR?=?0.22, 95% CI, 0.16-0.30) in COS/IUI cycles. Subgroup analysis results suggested statistically significant improvement in the CPR in non-PCOS patients (OR?=?1.54; 95% CI, 1.03-2.31) but not in the PCOS population (OR?=?1.65; 95% CI, 0.93-2.94) and multiple mature follicle cycles (OR?=?1.87; 95% CI, 0.27-12.66). There were no difference in the miscarriage and multiple pregnancy rates between the groups.

Conclusion

This meta-analysis suggested that GnRH-ant can reduce the incidence of PL and increase the CPR when used in COS/IUI cycles, and it was especially useful for non-PCOS patients. However, evidence to support its use in PCOS patients is still insufficient.

SUBMITTER: Luo S

PROVIDER: S-EPMC4192303 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.

Luo Shan S Li Shangwei S Jin Song S Li Ya Y Zhang Yaoyao Y

PloS one 20141009 10

<h4>Background</h4>Recent studies have indicated the use of gonadotropin-releasing hormone antagonists (GnRH-ant) as an adjuvant treatment to prevent premature luteinization (PL) and improve the clinical outcomes in patients undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI). However, the results of these studies are conflicting.<h4>Methods</h4>We conducted a systematic review and meta-analysis of randomized trials aiming to compare the clinical efficacy of GnRH ...[more]

PMID: 25299186

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Project description:BACKGROUND:Women with irregular menstruation should be considered to benefit from the ovarian stimulation. However, most literature did not separate ovulatory disorders from normal menstrual cycles. Our purpose was to assess the superiority of ovarian mild stimulation compared with the natural cycle in IUI for subfertile couples when the women with regular menstruation. METHODS:A retrospective study in a single medical center in which 2413 couples with 3573 IUI cycles were studied from 2013 to 2018. The results of IUI in natural cycles versus low-dose HMG induced cycles were analyzed. RESULTS:For young women (age?<?35?years) with normal menstrual cycle, HMG induced ovulation combined with IUI can improve clinical pregnancy outcome (13.55% in two follicular induced cycles vs. 7.23% in natural cycles, p?<?0.01); even if only one follicle was induced, the clinical pregnancy rate was increased to 10.32% (p?<?0.01). When two growth follicles were induced in HMG cycles, a remarkable improvement of the live birthrate (10.28% vs. 5.91% in natural cycles, p?<?0.05) was noted. Simultaneously, twin pregnancy rates were increased to 20.69% (p?<?0.01). Twin pregnancies showed significantly increased risk of both ectopic pregnancy and preterm birth (p?=?0.00 for both). For advanced women (age???35?years) with regular menstrual cycle, ovulation induction didn't improve clinical pregnancy and live birthrates, while age was the only relevant factor. CONCLUSIONS:Combining HMG induced ovulation and IUI can improve pregnancy outcome in young women with normal menstrual cycles. 1-2 follicles with diameter???14?mm served as the purpose of ovulation induction. Further, both twin and ectopic pregnancy rate in HMG cycles with two growth follicles were significantly higher than those in natural cycles were. Therefore, doctors must evaluate the risk before making choices and inform the patients to achieve the best results. For advanced women with normal menstrual cycles, natural IUI cycles were optional.

Project description:Can predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol?Common prognostic factors for high and low ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH.Predictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles.A retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial.Infertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis.In the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were prognostic for high ovarian response, and serum estradiol at stimulation Day 1 was associated with low ovarian response. The area under the receiver operating characteristic (ROC) curve (AUC) for the model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82 and 0.73; positive and negative predictive values were 0.40 and 0.95, respectively. The AUC for the model for a low ovarian response was 0.80. Sensitivity and specificity were 0.77 and 0.73, respectively; positive and negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of patients were high ovarian responders and 16.1% were low ovarian responders. The slope of the calibration line was 0.81 and 1.35 for high and low ovarian responses, respectively, both not statistically different from 1.0. In summary, common prognostic factors for high and low ovarian responses were female age, AFC and basal serum FSH and LH. Simple multivariable models are presented that are able to predict both a too low or too high ovarian response in patients treated with a GnRH antagonist protocol and daily rFSH.Anti-Müllerian hormone was not included in the prediction modelling.The findings will help with the identification of patients at risk of a too high or too low ovarian response and individualization of COS treatment.Financial support for this study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and B.M.J.L.M. was an employee of MSD at the time of development of this manuscript.NCT 00696800 and NCT00778999.

Project description:ObjectiveTo estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number.MethodsWe conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation.ResultsWe identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P<.01 and 0.2-10.6%, P<.01, respectively) when comparing one with five mature follicles present at the time of IUI (P<.01). In women younger than age 38 years with more than three follicles present, more than one quarter of all pregnancies were multiples. Similar findings occurred in women aged 38-40 years. In women older than age 40 years, up to four follicles tripled the odds of pregnancy (aOR 3.1, 95% CI 2.1-4.5) while maintaining a less than 12% risk of multiple gestation per pregnancy and a 1.0% absolute risk of multiples.ConclusionCaution should be used in proceeding with IUI after ovarian stimulation when there are more than two mature follicles in women younger than age 40 years owing to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.

Dataset Information

Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.

Background

Methods

Results

Conclusion

Publications

Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.

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