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ObjectiveGonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET.MethodsA total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups.ResultsEMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group.ConclusionAcupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

Background There are limited and controversial findings concerning ovulation induction using intrauterine and intramuscular human chorionic gonadotropin (hCG) injection compared to intramuscular hCG alone. The study aimed to examine the impact of intrauterine hCG injection, which is used to induce ovulation, on the efficacy of the intrauterine insemination (IUI) technique in patients with unexplained infertility. Methods A randomized controlled clinical trial was conducted involving 80 subjects with unexplained primary infertility at the infertility clinic of Al-Zahra Hospital in northwest Iran. Patients were randomly allocated into two groups: control and intervention. Both groups received initial treatment with letrozole and Recombinant follicle-stimulating hormone (r-FSH). After confirmation of at least one follicle measuring 18 mm or larger through ultrasonography, in the control group, two ampoules of 5000 units of hCG were administered intramuscularly. The intervention group received 500 units of hCG diluted in 0.5 cc of normal saline and was injected into the uterine cavity along with the two intramuscular ampoules. Primary outcomes were clinical and chemical pregnancy rates and the secondary outcome was any adverse pregnancy outcomes. Multiple logistic regression analysis was used to estimate crude and adjusted odds ratios (AORs) of the pregnancy rates with 95% confidence intervals (CIs). Results No significant differences were found between the two groups regarding baseline characteristics ( p  > 0.05). Chemical and clinical pregnancy rates in the control and intervention groups were (32.5 vs. 40%) (32.5% vs. 35%), respectively. In the final analysis after adjusting the potential confounders, intrauterine and intramuscular hCG injection increased the likelihood of chemical pregnancy by 1.39 times AOR = 1.42 (1.31–4.12; p  = 0.036), and clinical pregnancy by AOR = 1.25 (1.03–3.74; p  = 0.048) compared to intramuscular hCG alone. There were no statistical differences regarding adverse pregnancy outcomes between the study groups ( p value > 0.05). Conclusions It seems that ovulation induction through intrauterine and intramuscular hCG injection increased the odds of both chemical and clinical pregnancy rates compared with intramuscular hCG alone. Multicenter clinical trials and meta-analysis studies are needed for decision making in clinical settings.

Background The presence of submucous fibroids strongly impacts on IVF results, therefore, these patients should be considered for surgical or medical treatment. The aim of this study was to assess the role of Ulipristal acetate (UPA), a selective progesterone receptor modulator, in restoring uterine cavity deformation due to submucous fibroids, in infertile patients attempting an IVF treatment. The secondary study outcome was to evaluate the impact of preconception UPA treatment on rate of biochemical pregnancy, ongoing pregnancy, and live birth compared to a control group without fibroids. Methods Infertile patients with submucosal fibroid (Type 1 and Type 2 according to FIGO classification) were enrolled in the study as fibroids group and received 1 to 3 treatment cycles of UPA, according to their response, as reflected by fibroid volume reduction and restoration of normal uterine cavity. Patients in control group were randomly selected from a general IVF cohort by a ratio of 2:1 with fibroids group, matched by age, BMI, type and cause of infertility and antral follicle count. The impact of UPA on fibroids volume reduction was evaluated. IVF outcome was compared between groups. Results Twenty-six patients underwent UPA treatment revealed a mean volume reduction of their fibroids of 41%. A total of 15 (57.6%) biochemical pregnancy were obtained, resulting in 13 (50%) ongoing pregnancy and 9 (34.6%) healthy babies were already delivered. Similar results were obtained in control group. Conclusion Restoration of normal uterine cavity by UPA treatment prior to IVF treatment avoids surgery and establishes a pregnancy rate comparable to a control group without fibroids.

Background The optimal approach to luteal-phase support in infertility treatment remains a subject of debate. This study was conducted to investigate the clinical outcomes, side effects, and patient satisfaction associated with vaginal, subcutaneous, and intramuscular progesterone administration in infertile women undergoing Frozen Embryo Transfer (FET). Methods This three-armed randomized clinical trial assigned infertile patients eligible for FET to three progesterone treatment groups: vaginal suppositories (400 mg twice daily; n  = 100), subcutaneous injections (25 mg daily; n  = 102), and intramuscular injections (50 mg daily; n  = 108). The primary outcomes were chemical and clinical pregnancy rates per embryo transfer cycle, with chemical pregnancy defined as beta-human chorionic gonadotropin levels > 50 IU/mL two weeks post-transfer and clinical pregnancy confirmed by ultrasound four weeks later. Exploratory outcomes included progesterone-related adverse effects and participant satisfaction, assessed via a Likert-scale survey 12 weeks post-transfer. Statistical analyses included Chi-square tests for categorical data, one-way analysis of variances, and Kruskal–Wallis tests for continuous data. Results The intramuscular progesterone group had significantly higher chemical pregnancy rates compared to the vaginal and subcutaneous groups (41.7% vs. 26.0% and 27.5%, respectively; p  = 0.026). Although the clinical pregnancy rate was also higher in the intramuscular group (32.4%) compared to the vaginal (23.0%) and subcutaneous groups (21.6%), this difference was not statistically significant ( p  = 0.148). Additionally, patient satisfaction was greater with vaginal and subcutaneous applications than with intramuscular injections ( p  < 0.001), likely due to a significantly higher incidence of side effects, such as pain and edema at the injection site, in the intramuscular group ( p  < 0.001). Conclusions We found that intramuscular progesterone resulted in higher chemical pregnancy rates than vaginal or subcutaneous routes, but this did not translate into higher clinical pregnancy rates. Despite its effectiveness, intramuscular administration was associated with more adverse effects and lower patient satisfaction. Future research should explore optimizing progesterone regimens to balance efficacy and patient comfort. Trial registration The trial protocol was registered on December 6, 2020, in the Iranian Registry of Clinical Trials (IRCT), a primary registry in the World Health Organization (WHO) Registry Network, under the registration number IRCT20141217020351N12.

The objective of this study was to evaluate the effect of a stop gonadotropin-releasing hormone (GnRH) agonist with letrozole protocol in improving in vitro fertilization (IVF) cycles in poor ovarian responders (PORs) and to suggest a suitable new ovulation stimulation protocol for this group of infertile women. This randomized controlled trial was conducted at the Infertility Center of Taleghani Hospital, Tehran, Iran, from August 2024 to December 2024. The participants were 60 women who fulfilled the POSEIDON Group 4 criteria and had poor ovarian response in their previous IVF cycles. Participants were randomly assigned to the study and control groups and underwent a new IVF cycle. The study group underwent a new cycle with a stop agonist using the letrozole protocol, and the control group underwent the conventional stimulation protocol, which was the same as the previous cycle. Compared with the conventional protocol, the stop-GnRH agonist and letrozole protocols resulted in a significantly greater number of follicles >13 mm on the day of human chorionic gonadotropin (hCG) administration and a greater number of mature oocytes retrieved, with a significantly greater number of total embryos obtained at days 3 and 5 and a greater number of top-quality embryos. The mean biochemical and clinical pregnancy rates were similar between groups. The stop-GnRH agonist and letrozole protocol is a short and original protocol that seems to yield better outcomes for patients and may offer promising results for treating POSEIDON Group 4 patients with previous failed IVF.

Objective: To explore the impact of endometrial scratch injury (ESI) on intrauterine insemination (IUI) success. Methods: One hundred and fifty four infertile women received 100 mg of oral clomiphene citrate for 5 days starting on day 3 of the menstrual cycle. Patients were randomized to 2 equal groups: Group C received IUI without ESI and group S had ESI. Successful pregnancy was confirmed by ultrasound. Results: 13, 21, and 10 women got pregnant after the first, second, and third IUI trials, respectively, with 28.6% cumulative pregnancy rate (PR). The cumulative PR was significantly higher in group S (39%) compared to group C (18.2%). The PR in group S was significantly higher compared to that in group C at the second and third trials. The PR was significantly higher in group S at the second trial compared to that reported in the same group at the first trial but nonsignificantly higher compared to that reported during the third trial, while in group C, the difference was nonsignificant. Eight pregnant women had first trimester abortion with 18.2% total abortion rate with nonsignificant difference between studied groups. Conclusion: The ESI significantly improves the outcome of IUI in women with unexplained infertility especially when conducted 1 month prior to IUI.

Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth. In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful. A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity. ClinicalTrials.gov NCT02432209.

Background Poor ovarian response remains one of the biggest challenges for reproductive endocrinologists. The introduction of corifollitropin alpha (CFA) offered an alternative option to other gonadotropins for its longer half-life, its more rapid achievement of the threshold and higher FSH levels. We compared two different protocols with CFA, a long agonist and a short antagonist, and a no-CFA protocol. Methods Patients enrolled fulfilled at least two of the followings: AFC < 5, AMH < 1,1 ng/ml, less than three oocytes in a previous cycle, age > 40 years. Ovarian stimulation with an antagonist protocol was performed either with 300 UI rFSH and 150 UI rLH or 300UI HMG. In the long agonist group, after pituitary suppression with triptorelin, CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. In the short antagonist group CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. The primary objective was the effect on the number of oocytes and MII oocytes. Secondary objective were pregnancy rates, ongoing pregnancies and ongoing pregnancies per intention to treat. Results The use of CFA resulted in a shorter lenght of stimulation and a lower number of suspended treatments. Both the CFA protocols were significantly different from the no-CFA group in the number of retrieved oocytes ( p  < 0,05), with a non-significant difference in favour of the long agonist protocol. Both CFA groups yielded higher pregnancy rates, especially the long protocol, due to the higher number of oocytes retrieved ( p  < 0,05), as implantation rates did not differ. The cumulative pregnancy rate was also different, due to the higher number of cryopreserved blastocysts ( p  < 0,02). Conclusions The long agonist protocol with the addition of rFSH and rLH showed the best results in all the parameters. A short antagonist protocol with CFA was less effective, but not significantly, although provided better results compared to the no-CFA group. We suggest that a long agonist protocol with CFA and recombinant gonadotropins might be a valuable option for poor responders. Trial registration The study was approved by the local Ethics Committee (EudraCT2015–002817-31).

In this randomized trial, rates of vaginal birth of a healthy singleton at 2 years of follow-up were not higher among obese women who received a 6-month lifestyle intervention before infertility treatment than among those who received prompt infertility treatment. Obesity is a major public health problem. 1 In most developed countries, 14 to 20% of women of reproductive age are obese (body-mass index [BMI; the weight in kilograms divided by the square of the height in meters], ≥30), whereas in some countries, the prevalence of obesity is as high as 60%. 1 Obesity negatively affects female reproductive health because it is associated with increased risks of menstrual dysfunction, anovulation, and infertility. 2 – 4 Success rates with ovulation induction and assisted reproductive techniques are lower among obese infertile women than among normal-weight women. 5 , 6 The risks of miscarriage, 6 , 7 gestational diabetes, hypertensive disorders, . . .