Comparing the outcomes of in-vitro fertilization in patients receiving vaginal, subcutaneous, and intramuscular progesterone for luteal phase support: a three-armed randomized controlled trial.

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 sequential embryo transfer compared to blastocyst embryo transfer in in vitro fertilization (IVF) cycle in patients with the three repeated consecutive IVF. A randomized controlled trial.

The purpose of this study was to determine the pregnancy rate in the double sequential transfer of embryos on both day 3 and day 5 compared to day 5 alone, in in vitro fertilization-embryo transfer (IVF/ET) in patients with the three repeated consecutive IVF failures. In this controlled trial, women scheduled for IVF/ET with the three repeated consecutive IVF failures were randomized to either sequential transfer of embryos on day 2 and on day 5 after ovum pick-up (group 1, n = 60) or blastocyst ET on day 5 (group 2, n = 60) as a control group. The primary outcome measures were the chemical and clinical pregnancy rate. Baseline and cycle characteristics were comparable in both groups. Chemical and clinical pregnancy rate was similar in the sequential ET group (40%) compared to the day 5 of ET group (38.3%) (p value = .85). It seems that the double ET does not increase the chance of pregnancy rate compared to blastocyst ET on day 5 in the patients with the three repeated IVF-ET failures.

The effect of endometrial scratch injury on pregnancy outcome in women with previous intrauterine insemination failure: A randomized clinical trial.

AIM: Endometrial scratch injury (ESI) has been recently proposed to enhance the implantation rate in assisted reproductive technology cycles. The present study was conducted to determine the effect of ESI on pregnancy rate in women with intrauterine insemination (IUI) failure. METHODS: This prospective randomized controlled study was carried out in Imam-Khomeini Hospital and Royan Institute, Tehran, during a 12-month period from January 2013 to January 2014. After assessment, 169 patients who had IUI failure twice or more (no chemical or clinical pregnancy) with normal uterine anatomy and hysterosalpingography, were enrolled. They were randomly assigned into two groups. In the experimental group, all patients underwent ESI at day 8 or 9 of stimulation phase in the present IUI cycle, whereas no intervention was performed on the control group. IUI outcome was then compared between the two groups. RESULTS: A total of 150 patients completed the IUI cycle during the study. The chemical pregnancy rate was 10.7% and 2.7% in the experimental and control groups, respectively, without significant difference (P = 0.09). Also no significant differences were detected in terms of clinical pregnancy and miscarriage rates between the two groups (P > 0.05). CONCLUSIONS: No significant beneficial effect of ESI on fertility outcome in patients with repeated IUI failure was detected when it was carried out on day 8 or 9 of the same IUI stimulation cycle. Also, however, no negative impact secondary to ESI was observed. Therefore, confirmation or refutation of this hypothesis requires further studies with a larger sample size. IRCT201507271141N19.

Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation.

AIM: We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. METHODS: Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. RESULTS: Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p < 0.05], collected oocytes [13.5 (1.9) vs. 6.9 (0.5); p < 0.05] and AMH level [7.9 (0.7) vs. 3.6 (0.3); p < 0.05]. Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p < 0.001). The optimal cut point to discriminate poor response (oocytes ≤4) was 1.65 ng/ml ( AUC : 0.8; CI: 0.69-0.91; sensitivity: 89 % specificity : 71 %; and OR = 23.8 and P value <0.001). CONCLUSIONS: Iranian women with basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders.

Comparison of cabergoline and intravenous albumin in the prevention of ovarian hyperstimulation syndrome: a randomized clinical trial.

PURPOSE: To compare the efficacy of cabergoline (Cb2) and intravenous human albumin (HA) in the prevention of ovarian hyperstimulation syndrome. METHODS: In this randomized controlled trial study, 138 women who were at high risk for developing OHSS were randomly allocated into two groups. In Group one, 20 gr of HA 20% was infused over 1 h. Group two received 0.5 mg per day of Cb2 orally for 7 days, starting on oocyte pickup day. All patients were visited seven and 14 days after oocyte retrieval to determine early clinical or ultrasound evidence of OHSS. RESULTS: Moderate OHSS was observed in 33 versus 14 cases in the HA and Cb2 groups, respectively, which was significantly different. The number of severe OHSS cases in the HA group was significantly higher than in the Cb2 group (P < 0.001). CONCLUSIONS: Prophylactic oral low dose cabergoline was more effective and less costly than intravenous human albumin in the prevention of OHSS in high-risk patients.

Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients.

PURPOSE: To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle. MATERIALS AND METHODS: Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support. RESULTS: There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group. CONCLUSION: Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.

Assisted reproductive technique outcomes in hypogonadotropic hypogonadism women.

BACKGROUND AND OBJECTIVES: To evaluate the outcomes of using in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI cycle) techniques in hypogonadotropic hypogonadism (HH) women and comparing them to women with tubal factor infertility. DESIGN AND SETTINGS: Retrospective cohort study in Royan Institute, Iran. PATIENTS AND METHODS: Data from 81 HH patients treated with IVF/ICSI in the period from early 2009 until the end of 2010 were analyzed and compared with treatment results from 89 patients with tubal factor infertility. Moreover, data from the HH patients were analyzed with respect to the age factor. P value < .05 was considered statistically significant. The main outcome measures were implantation, fertilization, pregnancy, and live birth rates. RESULTS: Despite a higher fertilization rate and higher number of grade A/B embryos transferred in the tubal factor group, the implantation, pregnancy, and live birth rates were found to be similar between the 2 groups (P=.3, P=.1, P=.1, respectively). When the HH patients were evaluated according to the age factor, no significant difference was found regarding outcome parameters (P=.2). CONCLUSIONS: HH women that were treated with IVF/ICSI cycles seem to have a sound potential for pregnancy, even in advanced age patients.

Comparison of Intracytoplasmic Sperm Injection Outcomes between Oligozoospermic, Obstructive Azoospermic and Non-Obstructive Azoospermic Patients.

BACKGROUND: To determine the differences in sperm quality and results of intracytoplasmic sperm injection (ICSI) cycles between three groups of male factor infertile couples: oligozoospermic, obstructive azoospermic and non-obstructive azoospermic. MATERIALS AND METHODS: In this prospective cohort study, 628 male factor infertile couples who underwent ICSI cycles from April 2004 to March 2006 were enrolled. Three hundred fourteen oligozoospermic patients (group I), 180 obstructive azoospermic patients (group II) and 134 non-obstructive azoospermic patients (group III) were included. Fertilization, cleavage, implantation and clinical pregnancy, early abortion rates were assessed. Chisquare and analysis of variances with Post Hoc (Tukey test) were used for data analysis. RESULTS: Fertilization rates were significantly different in the three groups (group I: 66.6%; group II: 51.8%; group III: 47.7%; p=0.004). There were differences in the implantation rates (I: 19.5%; II: 17.6%; III: 6.4%; p=0.001). The cleavage rates were found to be 55.1% (group I), 47.5% (group II), 45.5%(group III), respectively. The clinical pregnancy rate was the lowest in the third group (I: 37.6%; II: 28.9%; III: 13.4%; p=0.001). There was no significant difference in early abortion rates between the three groups: (I: 10.7%; II: 9.8%; III: 8%; p=0.776). CONCLUSION: It can be concluded that patients with oligozoospermia may benefit the most from ICSI treatment. ICSI cycles which use spermatozoa from non-obstructive azoospermic patients have a lower chance for successful outcome. The results of this study suggest, in cases of failure to achieve pregnancy after 1 or 2 cycles in non-obstructive azoospermic patients, embryo donation would be a better alternative.