Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis.
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SUBMITTER: Wessel JA
PROVIDER: S-EPMC9434229 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis.
Wessel J A JA Danhof N A NA van Eekelen R R Diamond M P MP Legro R S RS Peeraer K K D'Hooghe T M TM Erdem M M Dankert T T Cohlen B J BJ Thyagaraju C C Mol B W J BWJ Showell M M van Wely M M Mochtar M H MH Wang R R
Human reproduction update 20220801 5
<h4>Background</h4>Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate ...[more]
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Project description:ObjectiveTo identify baseline characteristics of couples that are likely to predict conception, clinical pregnancy, and live birth after up to four cycles of ovarian stimulation with IUI in couples with unexplained infertility.DesignSecondary analyses of data from a prospective, randomized, multicenter clinical trial investigating pregnancy, live birth, and multiple pregnancy rates after ovarian stimulation-IUI with clomiphene citrate, letrozole, or gonadotropins.SettingOutpatient clinical units.Patient(s)Nine-hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.Intervention(s)As part of the clinical trial, treatment was randomized equally to one of three arms and continued for up to four cycles or until pregnancy was achieved.Main outcome measure(s)Conception, clinical pregnancy, and live-birth rates.Result(s)In a multivariable logistic regression analysis, after adjustment for other covariates, age, waist circumference, income level, duration of infertility, and a history of prior pregnancy loss were significantly associated with at least one pregnancy outcome. Other baseline demographic and lifestyle characteristics including smoking, alcohol use, and serum levels of antimüllerian hormone were not significantly associated with pregnancy outcomes.Conclusion(s)While age and duration of infertility were significant predictors of all pregnancy outcomes, many other baseline characteristics were not. The identification of level of income as a significant predictor of outcomes independent of race and education may reflect differences in the underlying etiologies of unexplained infertility or could reveal disparities in access to fertility and/or obstetrical care.Clinical trial registrationNCT01044862.
| S-EPMC4893990 | biostudies-literature
Project description:ObjectiveTo investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility.DesignSecondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI.SettingReproductive Medicine Network clinical sites.Patient(s)Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial.Intervention(s)Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved.Main outcomes measure(s)Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates.Result(s)A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids.Conclusion(s)No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility.Clinical trial registration numberNCT01044862.
| S-EPMC5472203 | biostudies-literature
Project description:BackgroundInformation available to date regarding the pregnancy outcomes of intrauterine insemination (IUI) without ovarian stimulation (OS) in infertile patients with unilateral tubal occlusion remains scarce. The objectives of this study were to investigate for couples affected by unilateral tubal occlusion (diagnosed via hysterosalpingography (HSG)/transvaginal real-time three-dimensional hysterosalpingo-contrast sonography (TVS RT-3D-HyCoSy)) and male infertility: (1) whether significant differences exist in pregnancy outcomes between IUI with or without OS cycles, and (2) whether the pregnancy outcomes of IUI without OS in women with unilateral tubal occlusion were similar to those of women with bilateral patent tubes.Methods258 couples affected by male infertility completed 399 IUI cycles. The cycles were divided into three groups: group A, IUI without OS in women with unilateral tubal occlusion; group B, IUI with OS in women with unilateral tubal occlusion; and group C, IUI without OS in women with bilateral patent tubes. The main outcome measures, including clinical pregnancy rate (CPR), live birth rate (LBR), and first trimester miscarriage rate, were compared between either groups A and B or groups A and C.ResultsAlthough the number of dominant follicles > 16 mm were significantly higher in group B than that in group A (group B vs. group A: 1.6 ± 0.6 vs. 1.0 ± 0.2, P < 0.001), the CPR, LBR, and first trimester miscarriage rate were comparable between these two groups. When comparing group C to group A, the duration of infertility was significantly longer in group C than that in group A (group A vs. group C: 2.3 ± 1.2 (year) vs. 2.9 ± 2.1 (year), P = 0.017). Except for the first trimester miscarriage rate, which was significantly higher in group A (42.9%, 3/7) than that in group C (7.1%, 2/28) (P = 0.044), no significant differences were observed in the CPR and LBR in these two groups. After adjusting for female age, body mass index, and the duration of infertility, similar results were obtained between groups A and C.ConclusionsIn couples affected by unilateral tubal occlusion (diagnosed via HSG/TVS RT-3D-HyCoSy) and male infertility, IUI without OS might be an alternative treatment strategy. However, when compared to patients with bilateral patent tubes, the patients with unilateral tubal occlusion showed a higher first trimester miscarriage rate following IUI without OS cycles. Further studies are warranted to clarify this relationship.
| S-EPMC10207788 | biostudies-literature
Project description:BackgroundIVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy.Objective and rationaleRandomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility.Search methodsWe searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool.OutcomesOf eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81-1.74, I2 = 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41-1.50, I2 = 0.0%).Wider implicationsThere is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making.
| S-EPMC10905504 | biostudies-literature
Project description: Not available
| S-EPMC11291944 | biostudies-literature
Project description:ObjectiveTo determine if chronic inflammation, assessed by basal high-sensitivity C-reactive protein (hs-CRP) levels, is associated with pregnancy outcomes in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination.DesignProspective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial.SettingMulticenter university-based randomized controlled trial.PatientsA total of 781 couples with unexplained infertility.InterventionsSecondary analysis.Main outcome measuresAdjusted risk ratios of live birth, clinical pregnancy, and pregnancy loss rates by hs-CRP levels.ResultsAssociations between hs-CRP levels and clinical pregnancy rates were not observed after adjustment for baseline body mass index. There were fewer live births among women with higher hs-CRP levels, although confidence intervals crossed 1.0. The risk of pregnancy loss was greater in women with increased hs-CRP levels (1-3 mg/L: risk ratio [RR], 1.67; 95% confidence interval [CI], 1.00-2.79; >3-10 mg/L: RR, 1.84; 95% CI, 1.06-3.20; and >10 mg/L: RR, 2.14; 95% CI, 1.05-4.36 compared to women with hs-CRP <1 mg/L).ConclusionsThis investigation suggests that chronic inflammation may increase the risk of pregnancy loss but not impact the clinical pregnancy rate in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Associations between inflammation and pregnancy outcomes in women with infertility merit further investigation.Clinical trial registration numberclinicaltrials.gov NCT01044862.
| S-EPMC8978106 | biostudies-literature
Project description:BackgroundSome studies have stated that intrauterine insemination (IUI) with controlled ovarian stimulation (COS) might increase the pregnancy rate, while others suggest that IUI in the natural cycle (NC) should be the first line of treatment. It remains unclear whether it is necessary to use COS at the same time when IUI is applied to treat isolated male factor infertility. Thus, we aimed to investigate efficacy of IUI with COS for isolated male factor infertility.MethodsA total of 601 IUI cycles from 307 couples who sought medical care for isolated male factor infertility between January 2010 and February 2020 were divided into two groups: NC-IUI and COS-IUI. The COS-IUI group was further divided into two subgroups according to the number of pre-ovulatory follicles on the day of HCG: cycles with monofollicular development (one follicle group) and cycles with at least two pre-ovulatory follicles (≥ 2 follicles group). The IUI outcomes, including clinical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and multiple pregnancy rates were compared.ResultsThe clinical pregnancy, live birth, spontaneous abortion, and ectopic pregnancy rates were comparable between the NC-IUI and COS-IUI group. Similar results were also observed among the NC-IUI, one follicle, and ≥ 2 follicles groups. However, with respect to the multiple pregnancy rate, a trend toward higher multiple pregnancy rate was observed in the COS-IUI group compared to the NC-IUI group (8.7% vs. 0, P = 0.091), and a significant difference was found between the NC-IUI and ≥ 2 follicles group (0 vs. 16.7%, P = 0.033).ConclusionIn COS cycles, especially in those with at least two pre-ovulatory follicles, the multiple pregnancy rate increased without a substantial gain in overall pregnancy rate; thus, COS should not be preferred in IUI for isolated male factor infertility. If COS is required, one stimulated follicle and one healthy baby should be the goal considering the safety of both mothers and foetuses.
| S-EPMC7977560 | biostudies-literature
Project description:ObjectiveTo characterize relationships associated with adverse endometrial development in patients undergoing IUI for unexplained infertility.DesignA retrospective review of 2,929 patients from 2004-2011.SettingLarge metropolitan infertility practice.Patient(s)Patients with unexplained infertility undergoing first IUI cycle at age less than 43 years, with a total motile sperm count ≥ 8 million.Intervention(s)Clomiphene citrate (CC) with FSH stimulation followed by IUI.Main outcome measure(s)Endometrial thickness, serum E2 (in picograms per milliliter) levels on the day of hCG trigger administration, body mass index (BMI) (in kilograms per meter squared), total motile sperm, follicle number, and clinical pregnancy.Result(s)Of the 2,929 patients who met the inclusion criteria, 466 (15.9 %) achieved a clinical pregnancy. Pregnancy rates (PRs) increased significantly with increasing endometrial thickness on the day of hCG administration and with increasing serum E2 level, but were not significantly related to age, BMI, or follicle numbers according to multiple logistic regression modeling. Peak endometrial thickness declined with age and increasing E2 levels. The BMI was associated with thicker endometrium, but it was also associated with lower peak E2 levels.Conclusion(s)The impact of "endometrial factor" infertility may be underappreciated in IUI therapy. Targeted therapies to optimize the endometrium represent an important new area to improve in current fertility success rates.
| S-EPMC3760031 | biostudies-literature
Project description:ObjectiveTo identify risk factors for pregnancy outcomes in couples treated with intracervical or intrauterine insemination, with or without superovulation for unexplained or male-factor infertility.DesignSecondary analysis of data from a randomized superovulation and intrauterine insemination trial.SettingAcademic medical centers.Intervention(s)Treatment continued for four cycles unless pregnancy was achieved.Patient(s)Out of 932 couples randomized to four treatment groups, 664 couples who had completed the lifestyle questionnaires were assessed for occurrence of pregnancy and live birth.Main outcome measure(s)Pregnancy and live birth.Result(s)The pregnancy and live birth rates were significantly higher in couples in which the female partners reported that they had consumed coffee or tea in the past or drank alcoholic beverages in the past (past users) compared with those who had never consumed coffee, tea, or alcoholic beverages. Past users also had significantly higher pregnancy and live birth rates than those currently consuming coffee or tea or alcoholic beverages. Demographic, occupational exposure, and other lifestyle factors were not significant.Conclusion(s)Couples in which the female partners drank coffee, tea, or alcoholic beverages in the past had higher pregnancy and live birth rates compared with never or current users. When discontinuing these habits, they might have made other lifestyle changes to improve the pregnancy outcome.
| S-EPMC3319287 | biostudies-literature
Project description:BackgroundRecent 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.MethodsWe 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.ResultsMeta-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.ConclusionThis 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.
| S-EPMC4192303 | biostudies-literature