Comparison of luteal phase stimulation with follicular phase stimulation in poor ovarian response: a single-blinded randomized controlled trial.

BACKGROUND: In the last decade, luteal-phase ovarian stimulation (LPOS) has been suggested as an alternative controlled ovarian stimulation (COS) protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles mainly in women with a history of poor ovarian response (POR). The present randomized controlled trial study aimed to compare the outcomes of follicular phase ovarian stimulation (FPOS) and LPOS protocols in POR cases undergoing ICSI cycles. METHODS: Seventy-eight POR patients who met the Bologna criteria and underwent an ICSI cycle were included. In this study, 39 POR cases were allocated to the FPOS group, and 39 POR cases were allocated to the LPOS group. The primary outcome was the number of metaphase II (MII) oocytes. In addition, the total number of oocytes, number of top-quality day 3 embryo, day 3 embryo development rate, chemical pregnancy and clinical pregnancy rates were defined as secondary outcomes. RESULTS: The obtained results demonstrated that the number of MII oocytes significantly increased in the LPOS group compared to the FPOS group (P = 0.007). However, there was no significant difference between the two groups regarding the number of GV and MI oocytes, number of top-quality day 3 embryos and day 3 embryo development rate among both categories of patients. Also, the number of total and MII oocytes was significantly higher in the LPOS group (P = 0.016). CONCLUSION: These results suggest that LPOS protocol effectively increases the number of mature oocytes in women with a history of POR. TRIAL REGISTRATION: IRCT20210405050852N1 (Registered at Iranian registry of clinical trials; available at https://en.irct.ir/trial/55402 ).

The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response.

BACKGROUND: Assisted reproduction faces a significant obstacle in the form of poor ovarian response (POR) to controlled ovarian stimulation. To address this challenge, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. Our previous research has demonstrated that menstrual blood-derived-mesenchymal stromal cells (MenSCs) injected into the ovaries of women with POR can increase pregnancy rates. The objective of this study was to examine whether MenSC therapy could enhance ovarian reserve parameters and pregnancy outcomes in a larger population of individuals with POR. METHOD: This study consisted of 180 infertile individuals with POR who declined oocyte donation. Participants were divided into two groups: those who received bilateral MenSCs intraovarian injection and those who received no intervention. Our primary aim was to compare the rates of spontaneous pregnancy between the two groups, followed by an investigation of any alterations in the ovarian reserve parameters, such as serum FSH, AMH, and AFC levels, as well as the ICSI/IVF outcomes, in both groups of participants. RESULTS: The MenSC therapy exhibited a favourable tolerability profile and did not raise any safety concerns. Following the 2-month follow-up period, women who received MenSC treatment demonstrated a significantly higher rate of spontaneous pregnancy (P < 0.005) and an improvement in anti-Müllerian hormone (AMH) levels (P = 0.0007) and antral follicle count (AFC) (P < 0.001), whereas the control group demonstrated a considerable decline in these parameters (Both P < 0.001). The MenSC therapy led to a greater number of mature oocytes and embryos among women who underwent ICSI/IVF. Our age subgroup analysis demonstrated a significant difference in the number of spontaneous pregnancies and ICSI/IVF outcomes between the treatment and control groups only among individuals below 40 years of age. CONCLUSION: The results of our study indicate that MenSCs treatment may be a viable option for treating women experiencing POR. However, in order to be widely implemented in clinical practice, the clinical effectiveness of MenSCs therapy will need to be established through rigorous prospective randomized clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308 . IRCT, IRCT20180619040147N4. Registered 08/01/2020.

Perception of Female Identity in Women with Premature Ovarian Insufficiency: A Qualitative Study.

Background: Premature ovarian insufficiency (POI) occurs in women before the age of 40. Although the outcomes of POI in women include its adverse effects on general health, sexual-reproductive health, and finally reduced quality of life. One of the first adverse consequences is a threat to female identity of the patients. The purpose of the present study was to investigate the perception and experience of women with POI about female identity. Methods: In this qualitative study, interviews were conducted with 15 women having POI. Data included participants' recorded voices that were analyzed using conventional content analysis. Results: After content analysis of the interviews with a focus on the perception and experience of women with POI about female identity, four categories emerged; they included the failure in realization of motherhood dream, the importance of menstruation, construction of female identity, and attempts to normalize the situation. Conclusion: After analyzing the emerged categories obtained by interviewing with POI women, it seems that physicians need to pay special attention to the distortion of the female identity of these patients and educate the medical team about the importance of the effect of treatment on improving their emotional health.

Intraovarian Administration of Autologous Menstrual Blood Derived-Mesenchymal Stromal Cells in Women with Premature Ovarian Failure.

BACKGROUND: Premature ovarian failure (POF) is a well-known cause of infertility, particularly in women under the age of 40. POF is also associated with elevated gonadotropin levels, amenorrhea and sex-hormone deficiency. AIM OF THE STUDY: In this study, the therapeutic potential of autologous mesenchymal stromal cells obtained from menstrual blood (Men-MSCs) for patients with POF was evaluated. METHODS: 15 POF patients were included in the study. The cultured Men-MSCs were confirmed by flow cytometry, karyotype, endotoxin and mycoplasma and were then injected into the patients' right ovary by vaginal ultrasound guidance and under general anesthesia and aseptic conditions. Changes in patients' anti-Müllerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone (FSH), luteal hormone (LH), and estradiol (E2) levels, as well as general flushing and vaginal dryness were followed up to one year after treatment. RESULTS: All patients were satisfied with a decrease in general flushing and vaginal dryness. 4 patients (2.9%) showed a spontaneous return of menstruation without additional pharmacological treatment. There was a significant difference in AFC (0 vs. 1 ± 0.92 count, p value ≤0.001%), FSH (74 ± 22.9 vs. 54.8 ± 17.5 mIU/mL, p-value ≤0.05%), E2 (10.2 ± 6 vs. 21.8 ± 11.5 pg/mL p-value ≤0.01%), LH (74 ± 22.9 vs. 54.8 ± 17.5 IU/L,p-value ≤0.01%) during 3 months post-injection. However, there were no significant changes in AMH (p-value ≥0.05%). There were also no significant differences in assessed parameters between 3 and 6 months after cell injection. CONCLUSION: According to the findings of this study, administration of Men-MSCs improved ovarian function and menstrual restoration in some POF patients.

The effect of low-molecular-weight heparin on live birth rate of patients with unexplained early recurrent pregnancy loss: A two-arm randomized clinical trial.

Background: The effect of anticoagulant medication in unexplained early recurrent pregnancy loss (RPL) patients is controversial. This clinical trial evaluated the effect of low-molecular-weight heparin (LMWH) on pregnancy outcomes in these patients. Materials and Methods: The study was performed as a single-blind randomized clinical trial between 2016 and 2018. Samples were selected from patients who were referred to Avicenna RPL clinic with a history of at least two previously happened early unexplained miscarriages. The eligibility was defined strictly to select unexplained RPL patients homogenously. One hundred and seventy-three patients who got pregnant recently were allocated randomly into two groups LMWH plus low-dose aspirin treatment (Group A = 85) and low-dose aspirin treatment only (Group B = 88)) and were followed up till their pregnancy termination (delivery/abortion). A per-protocol analysis was carried out and all statistical tests were two-sided with a P < 0.05 significance level. Results: The live birth rates (LBRs) in Groups A and B were 78% and 77.1%, respectively, which did not show any statistically significant difference between the two groups, neither in rates nor in time of abortion. In subgroup analysis for polycystic ovary syndrome (PCOS) patients, the odds ratio for study outcome (intervention/control) was 2.25 (95% confidence interval: 0.65-7.73). There was no major adverse event whereas minor bleeding was observed in 18% of patients in Group A. Conclusion: LMWH does not improve the LBR in unexplained RPL patients, however, it is recommended to evaluate its effect separately in PCOS patients.

Effects of Adjuvant Growth Hormone Therapy on Poor Ovarian Responders in Assisted Reproductive Technology.

Objective:The present study aimed to evaluate the effect of adjuvant growth hormone (GH) therapy in antagonist protocol aiming to improve ovarian response and clinical outcomes of women with poor ovarian response. Methodology:This clinical trial was a single-center study, controlled with equal randomization, which was carried out in Avicenna Infertility Clinic, Tehran, Iran. Totally, 118 patients were randomly allocated to either the intervention or the control group. The intervention group received GH and gonadotropin in gonadotropin-releasing hormone (GnRH) antagonist protocol (GH/GnRHant), while the control group received gonadotropin in GnRH antagonist protocol (GnRHant). Results:The results revealed that the number of days of gonadotropin administration significantly decreased (p-value = 0.040) in the GH/GnRHant group compared to the GnRHant group. Also, our study findings showed that a number of top-quality day 3 embryos and clinical pregnancy rate were higher in the GH/GnRHant group (p-value = 0.007) compared to the GnRHant group (p-value = 0.036). However, there was no significant difference between the two groups in terms of number of received gonadotropin ampoules, number of retrieved MI and MII oocytes, chemical pregnancy rate, ongoing pregnancy rate and live birth rate. Conclusion:These results suggest that adjuvant GH therapy in antagonist protocol in women with a history of poor ovarian response is effective to decrease the number of days of received gonadotropin ampoules and improve pregnancy rate.

Effects of Autologous Platelet-Rich Plasma in women with repeated implantation failure undergoing assisted reproduction.

OBJECTIVE: Repeated implantation failure (RIF) is a major challenge in reproductive medicine. On the other hand, there has not yet been established a confirmed outcome regarding the usage of platelet-rich plasma (PRP) in women undergoing intracytoplasmic injection (ICSI) or in-vitro fertilization (IVF); hence, the objective of this study was to evaluate the effect of the intrauterine infusion of PRP on pregnancy outcomes in women undergoing ICSI. METHODS: In this prospective double-blind clinical trial, 100 women with at least two previous unexplained RIF, who were candidates for frozen-thawed embryo transfer, were allocated into two groups. One subgroup of patients was treated by intrauterine infusion of PRP (0.5CC, contained platelet 4-5 times more than a peripheral blood sample, which was performed 48 hours before blastocyst transfer) and the other subgroup was treated by intrauterine catheterization only. We compared the implantation rates between the two groups. RESULTS: The pregnancy rate was 20% in the intervention subgroup, while in the control subgroup it was 13.33%; therefore, there was a significant statistical difference between the two groups. CONCLUSIONS: According to this paper, PRP could be successful in improving the pregnancy outcome in RIF patients, and we highly recommend other studies with larger samples to confirm the PRP therapy efficacy in RIF patients.

Perceptions and experiences of women with premature ovarian insufficiency about sexual health and reproductive health.

BACKGROUND: Premature ovarian insufficiency (POI) is a condition with impaired ovarian function that occurred in women before the age of 40. Considering that women with POI are in reproductive age and their fertility and sexual life are afflicted by this disorder directly, the present study aimed to investigate perception and experience of women with POI of sexual and reproductive health (SRH). METHODS: This is a qualitative that was implemented based on the conventional content analysis approach. The data were collected using semi-structured in-depth interviews with 16 women having POI, based on purposeful sampling and continued until data saturation. The participants were women with POI that referred to the three infertility center in Tehran, Iran. The audio recorded data were transcribed verbatim and then analyzed using conventional content analysis based on the method proposed by Zhang and Wildmouth. RESULTS: After content analysis of the interviews with a focus on the perception and experience of women with POI of SRH, four main categories emerged i.e. endangerment of women's health, psychological agitation, disruption of social life and disturbance in sexual life. CONCLUSION: POI affects different aspects of women SRH (women physical, psychological, social and sexual heath). Therefore, knowledge of patients' concerns by health professionals is helpful to improve service delivery and increasing the effectiveness of treatment interventions by a comprehensive health care attitude.

Improvement of Pregnancy Rate and Live Birth Rate in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived- Mesenchymal Stromal Cells: Phase I/II Clinical Trial.

The study was aimed to evaluate the safety and efficacy of cell therapy using autologous menstrual blood derived- mesenchymal stromal cells (Men-MSCs) in fertility potential of poor ovarian responders (PORs). POR women were divided into mesenchymal stroma cell (MSC) therapy (n = 15) and routine ICSI (n = 16) groups. The cultured Men-MSCs were autologously injected into left ovary of MSC group after approval by flow cytometry, karyotyping, endotoxin, sterility and mycoplasma tests. Changes in anti-Mullerian hormone (AMH), antral follicles count (AFC), oocytes and embryos number, clinical pregnancy rate and live birth rate were followed in both groups up to one year after treatment. 4 of 15 participants in MSC group got naturally pregnant during 3 months after cell administration, in contrast to no natural conception in control group (P = 0.04). The mean AMH level did not significantly differ with that of previous cycle or control group. Although mean AFC and oocytes number in MSC group did not indicate considerable difference with those of control group, raise of these parameters in comparison with previous cycle was significant (both P = 0.01). Nonetheless, oocyte fertilization rate and embryo number in MSC group were higher than control group (P = 0.04 and P = 0.008, respectively). Altogether, 7 of 15 women in MSC group and 2 of 16 women in routine ICSI group had clinical pregnancy that resulted in 5 live births in main group and one birth in control group. In conclusion, cell therapy using Men-MSCs could be considered as a potential treatment to restore fertility capability of POR women.The trial registration number (TRN): IRCT20180619040147N2.Date of registration: 2018-08-21.

Effects of silymarin, cabergoline and letrozole on rat model of endometriosis.

OBJECTIVE: Silymarin as an herbal drug has potent antioxidant effects that could make it a good choice for endometriosis therapy. The aim of the current study was to determine the effects of silymarin as an herbal drug on induced endometrial lesion in rat model of endometriosis. MATERIALS AND METHODS: A total of 32 mature, female Sprague-Dawley rats were allocated into 4 experimental groups. The duration of study was about 6 months. Endometriosis implants were surgically prepared and autografted into 32 rats. Three weeks after endometriosis induction, animals were randomly allocated into four groups: Group 1 received cabergoline (CAB group); Group 2 received letrozole (LET group); Group 3 received silymarin (SIL group) and Group 4 received no medication (CONT group). Experimental groups were treated for 3 weeks and then were sacrificed for volume and histopathological evaluation of implants and biochemical assessment. Serum and peritoneal levels of vascular endothelial growth factor (VEGF), total antioxidant activity (TAC) and tumor necrosis (TNF)-α were measured. RESULTS: Mean volume of the implants decreased significantly in silymarin (p < 0.001), letrozole (p < 0.001) and cabergoline (p < 0.001) groups compared to the control. Histopathologic score was significantly lower in silymarin (p: 0.039), letrozole (p: 0.017) and cabergoline (p < 0.001) groups compared to the control. Those receiving silymarin had significantly higher serum TAC compared to control after 21 days of therapy (p < 0.001). CONCLUSION: Silymarin, Letrozole, and Cabergoline administration resulted in decreased size and histopathologic grade of the induced endometrial lesions in a rat model. Silymarin appears to be a virtual novel therapeutic agent for treatment of endometriosis.

Efficacy of Intrauterine Injection of Granulocyte Colony Stimulating Factor (G-CSF) on Treatment of Unexplained Recurrent Miscarriage: A Pilot RCT Study.

BACKGROUND: Endometrium undergoes several changes in structure and cellular composition during pregnancy. Granulocyte Colony-stimulating Factor (GCS-F) is an important cytokine with critical role in embryo implantation and pregnancy. The aim of the present study was to evaluate the impact of intrauterine injection of G-CSF in patients who suffer from unexplained recurrent miscarriage (RM). METHODS: In the present randomized clinical trial, a total of 68 patients were randomly allocated into two study groups including intrauterine G-CSF (n=23, 300 µg) injection and control group (n=27, no G-CSF injection). Eighteen out of 68 patients were excluded from the final analysis due to different reasons. All patients were in Ovulation Induction (I/O) cycle. In G-CSF group, intrauterine injection of G-CSF was done twice in the cycle. All enrolled patients were under 40 years old and had at least two unexplained pregnancy losses. Pregnancy was evaluated by titer of ßhCG, presence of gestational sac (implantation) and fetal heart rate (clinical pregnancy) was assessed by vaginal ultrasonography. Student's T test and Mann-Whitney U were used for analysis. The p≤0.05 was determined as statistically significant. RESULTS: No significant differences were observed between the two study groups when the rates of chemical pregnancy (26.1% vs. 29.6%, p=0.781), implantation (26.1% vs. 22.2%, p=0.750), clinical pregnancy (17.4% vs. 11.1%, p=0.689) and abortion (33% vs. 37.5%, p=0.296) were compared. CONCLUSION: In our study, no significant difference was observed between the two study groups when the rates of chemical pregnancy, implantation, clinical pregnancy and abortion were compared.

Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Outcome of ICSI-ET Cycles in Women with Previous History of IVF/ICSI Failure: A Randomized Controlled Trial.

BACKGROUND: GnRH agonist administration in the luteal phase has been suggested to beneficially affect the outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This blind randomized controlled study evaluates the effect of GnRH (Gonadotropine Releasing Hormone) agonist administration on ICSI outcome in GnRH antagonist ovarian stimulation protocol in women with 2 or more previous IVF/ICSI-ET failures. METHODS: One hundred IVF failure women who underwent ICSI cycles and stimulated with GnRH antagonist ovarian stimulation protocol, were included in the study. Women were randomly assigned to intervention (received a single dose injection of GnRH agonist (0.1 mg of Decapeptil) subcutaneously 6 days after oocyte retrieval) and control (did not receive GnRH agonist) groups. Implantation and clinical pregnancy rates were the primary outcome measures. RESULTS: Although the age of women, the number of embryos transferred in the current cycle and the quality of the transferred embryos were similar in the two groups, there was a significantly higher rate of implantation (Mann Whitney test, p = 0.041) and pregnancy (32.6% vs. 12.5%, p = 0.030, OR = 3.3, 95%CI, 1.08 to 10.4) in the intervention group. CONCLUSION: Our results suggested that, in addition to routine luteal phase support using progesterone, administration of 0.1 mg of Decapeptil 6 days after oocyte retrieval in women with previous history of 2 or more IVF/ICSI failures led to a significant improvement in implantation and pregnancy rates after ICSI following ovarian stimulation with GnRH antagonist protocol.

ART Outcomes in GnRH Antagonist Protocol (Flexible) and Long GnRH Agonist Protocol during Early Follicular Phase in Patients with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

BACKGROUND: Since increased LH in the early follicular phase in PCOS patients especially in GnRH antagonist protocol could be associated with reduced oocyte quality and pregnancy and impared implantation. The current study was conducted to determine ART outcomes in GnRH antagonist protocol (flexible) and long GnRH agonist protocol and compare them with adding GnRH antagonist in GnRH antagonist (flexible) protocol during early follicular phase in patients with polycystic ovary syndrome undergoing ICSI. METHODS: In this randomized clinical trial, 150 patients with polycystic ovary syndrome undergoing ICSI were enrolled from 2012 to 2014 and randomly assigned to receive either GnRH antagonist protocol during early and late follicular phase or GnRH antagonist protocol (flexible) or long GnRH agonist protocol. The clinical and laboratory pregnancy in three groups was determined and compared. In this context, the chi-square and Fisher's exact test and ANOVA were used for data analysis. Statistical significance was defined as p<0.05. RESULTS: There was no statistically significant difference with respect to chemical pregnancy and clinical pregnancy between the three groups. Also, other indices such as number and quality of oocytes and embryos were alike. CONCLUSION: Totally, according to our results, GnRH antagonist protocol during early and late follicular phase and GnRH antagonist protocol (flexible) and long GnRH agonist protocol in patients with polycystic ovary syndrome undergoing ICSI are similarly effective and use of each one based on patients' condition and physicians' opinion could be considered.