The effect of adding L-Carnitine to the GnRH-antagonist protocol on assisted reproductive technology outcome in women with polycystic ovarian syndrome: a randomized clinical trial.

OBJECTIVE: This study aimed to investigate the effect of adding L-Carnitine to the gonadotropins on ART outcome in frozen-thawed embryo transfer cycles among PCOS women. METHODS: In this randomized clinical trial, 83 patients with PCOS were randomized to either L-Carnitine supplemented (n = 42) or control (n = 41) groups. The L-Carnitine group was given 3000 mg of oral L-Carnitine daily until the final day of ovulation. The numbers of metaphase II (MII) oocytes, 2-pronuclears (2PNs), oocyte maturity rate, fertilization rate, fertilization proportion as well as implantation, chemical and clinical pregnancy rates were compared between the two groups. RESULTS: Even though the duration of stimulation and endometrial thickness were comparable between groups (p > .05), serum estradiol level on the day of oocyte triggering, was significantly higher in the L-Carnitine group compared to the control group (p < .05). In contrast, the number of retrieved and MII oocytes as well as the number of 2PNs and obtained embryos were similar between groups (p > .05). Moreover, oocyte maturity rate (0.85 ± 0.38 vs. 1.02 ± 0.90), fertilization proportion (0.62 ± 0.44 vs. 0.80 ± 0.86), fertilization rate (0.70 ± 0.22 vs. 0.76 ± 0.19) along with implantation rate (18.1 vs. 13.7%), chemical (26.8 vs. 30.7%) and clinical (24.3 vs. 25.6%) pregnancy rates, were all comparable between L-Carnitine and control groups respectively (p > .05). CONCLUSIONS: Our result showed that oral L-Carnitine administration during induction of ovulation among PCOS women could not improve laboratory and pregnancy outcome.

Frozen-thawed cleavage stage versus blastocyst stage embryo transfer in high responder patients.

Clinical outcomes following frozen-thawed cleavage embryo transfer versus frozen-thawed blastocyst transfer in high responder patients undergoing in vitro fertilisation/intracytoplasmic sperm injection cycles are still debated. In a retrospective study, 106 high responder patients who were candidate for 'freeze-all embryos' were recruited. Frozen-thawed embryos were transferred at the cleavage stage (n = 53) or the blastocyst stage (n = 53). Clinical pregnancy was considered as the primary outcome and chemical pregnancy, ongoing pregnancy, implantation rate, and fertilization rate, as well as miscarriage rate, were measured as the secondary outcome. Clinical (47.2% vs. 24.5%), chemical (56.6% vs. 32.1%), and ongoing pregnancy rates (37.7% vs. 17%) as well as implantation rates (33.6% vs. 13.5%) were significantly higher in the blastocyst group compared with the cleavage group respectively (P < 0.05). Miscarriage rate was comparable between groups (P > 0.05). Transfer of frozen-thawed embryos at the blastocyst stage was preferable in the high responder patients to increase implantation, pregnancy and live birth rates compared with cleavage stage embryo transfer.

Role of granulocyte colony-stimulating factor in human reproduction.

As new research reveals, granulocyte colony-stimulating factor (G-CSF) plays an effective role in pregnancy success, considering that it not only affects the embryo implantation and ovarian function but also it promotes endometrial thickening and improves the pathophysiology of endometriosis, which all fundamentally lead to reducing pregnancy loss. In this review, we focus on the role of G-CSF in human reproduction. We summarized its role in ovulation, luteinized unruptured follicle syndrome, poor responders, improving repeated in vitro fertilization failure, endometrial receptivity and treatment of thin endometrium, and recurrent spontaneous abortion.

Religious experiences of Iranian transgenders: A qualitative study.

BACKGROUND: Gender identity disorder and its treatment with sex reassignment surgery is a profound experience, which can affect the mental, interpersonal, social and religious aspects of one's life. METHODS: This was a qualitative content analysis study focusing on the various dimensions of the experiences of seven patients suffering from gender identity disorder in a female-to-male subgroup. This study presents a report concerning the religious aspects of their experience. RESULTS: The findings of this study were categorized into the four following conceptual categories: sense of guilt; accomplishing a sense of submission to God's will as well as God's pleasing; practical commitment to religion; and rejection by the religious communities. CONCLUSION: Diminishing religion to spirituality comprised the core experiences of these patients having intimate relations with such concepts as secularism, stigma, and technocracy.

Effectiveness of Autologous Platelet-Rich Plasma Therapy in Women with Repeated Implantation Failure: A Randomized Clinical Trial.

BACKGROUND: Platelet-rich plasma (PRP) therapy has been shown to enhance tissue regeneration by expressing several cytokines and growth factors (GFs). This study investigated the effect of intrauterine infusion of PRP as a noninvasive autologous GF on pregnancy outcomes in women with repeated implantation failure. MATERIALS AND METHODS: This randomized clinical trial was conducted to compare the pregnancy rates between two groups of women who were candidates for the frozen-thawed embryo transfer with a history of two or more implantation failures. The PRP group (n=33) was treated with hormone replacement therapy+0.5 cc to 1 cc PRP infused into the uterine cavity two days before the embryo transfer. The control group (n=33) was only treated with hormone replacement therapy. The endometrial preparation process was done similarly in both groups. The chemical, clinical, and ongoing pregnancy, and implantation rates were compared between the two groups. RESULTS: Our results showed that the chemical pregnancy rate was not statistically higher in the PRP group in comparison with the control group (36.4 vs. 24.2%). In addition, the clinical pregnancy, ongoing pregnancy, and implantation rates were higher in the PRP group than the control group; however, the difference between the two groups was not statistically significant. CONCLUSION: Administration of intrauterine PRP before embryo transfer in women with repeated implantation failure (RIF) does not affect assisted reproductive technology (ART) outcomes (registration number: IRCT2016090728950N3).

The Effect of Uterine Length Measurement before Embryo Transfer versus Transabdominal Ultrasound-Guided Embryo Transfer on FET Cycle Outcome: A Randomised Clinical Trial.

BACKGROUND: Embryo transfer (ET) is an important step in assisted reproductive technology. Uterine length measurement before ET (ULMbET) enables the determination of catheter length and anatomical variation before the ET. Therefore, in this study, we aim to compare ULMbET and transabdominal ultrasound-guided ET (TAUGET). MATERIALS AND METHODS: This open-label randomised clinical trial enrolled 264 women who were scheduled for frozen- thawed ET (FET) cycles. The women were randomised to the ULMbET or TAUGET group for ET. The primary outcome of this study was clinical pregnancy. RESULTS: A total of 132 women were randomly assigned to the ULMbET group and 132 women to the TAUGET group. However, four women in the ULMbET group did not receive the allocated method after randomisation. Finally, 128 women from the ULMbET group and 132 women from the TAUGET group were assessed. No statistically significant differences existed in chemical pregnancy rate (31.3 vs. 36.4%, P=0.384), clinical pregnancy rate (23.4 vs. 28%, P=0.397), and implantation rate (15 vs. 17.8%, P=0.401) between the ULMbET and TAUGET groups, respectively. CONCLUSION: The results of this clinical trial show no differences in pregnancy outcomes in FET cycles following ULMbET and TAUGET (registration number: IRCT20110509006420N240).

Intrauterine autologous platelet-rich plasma treatment in women with at least two implantation failures: A retrospective cohort study.

Background: Finding the most effective way to improve implantation rate in women who are receiving assisted reproductive technology treatment is still a challenge. Objective: This study aimed to assess the pregnancy outcomes of intrauterine platelet-rich plasma (PRP) therapy in women with a history of at least 2 implantation failures. Materials and Methods: In this retrospective cohort study, data of 852 women who were candidates for frozen-thawed embryo transfer was extracted from their medical records from April 2017 to September 2021 at Yazd Reproductive Sciences Institute, Yazd, Iran. Of these, 432 received intrauterine PRP treatment 48 hr before transfer (PRP group), and the results of the pregnancy outcomes compared with 420 of the control group who did not receive the treatment before transfer. Results: Pregnancy outcomes, including chemical, clinical, ongoing pregnancy, and live birth rate were statistically significant in the PRP group (p < 0.001). However, when categorized according to the implantation history, this significant improvement in all 4 was only seen in women with at least 2 prior implantation failures. In women with a history of only one implantation failure, PRP therapy significantly improved the ongoing pregnancy and live birth rate (19.5%, p = 0.04). Also, in women who received donor eggs and had repeated implantation failure, PRP improved pregnancy outcomes clinically but not statistically (p = 0.15). Conclusion: PRP seems to be effective in improving the pregnancy rate in women with a history of 2 or more implantation failures and also shows an increase in the live birth rate in women with only one implantation failure.

The report of ovarian tissue transplant in Iran: A case report.

Background: Cancer treatments such as chemotherapy and radiotherapy increase the chance of ovarian failure. Ovarian tissue transplantation (OTT) is a viable option for fertility preservation in these cases. We aim to report ovarian transplantation in a leukemia case undergoing the vitrification method. Case Presentation: The case was a 28-yr-old female in Research and Clinical Center for Infertility, Yazd, Iran who was suffering from leukemia. Ovarian biopsy was performed by laparoscopy surgery and transported to cryopreservation lab at 4 C for 1-2 hr. The ovarian cortex was removed from the medulla, and ovarian strips were cryopreserved by vitrification. This procedure used the equilibration and vitrification solutions including medium 199 supplemented with 20% serum, and ethylene glycol and dimethyl sulfoxide with concentrations of 7.5% and 20%, respectively. Before doing OTT, we assessed the tissue viability and follicular count by chick embryo chorioallantoic membranes and histologic survey, respectively. OTT was done after complete remission, following warmed tissue sutured together and transplanted on the residual medulla on the right side. On the left side, the ovary was removed completely; however, 2 strips were put on the peritoneal pocket. Anti-Müllerian hormone, follicle-stimulating hormone, and luteinizing hormone levels were 0.1 ng/mL, 36.5 mIU/mL, and 19.8 mIU/mL before OTT. During a 6-month follow-up, the anti-Müllerian hormone increased to 0.9, and then follicle-stimulating hormone and luteinizing hormone levels decreased dramatically until 17.47 mIU/mL and 6.71 mIU/mL, respectively. Also, the patient had 3 cycles of menstrual periods. Conclusion: We demonstrated an appropriate hormonal profile, and the restoration of the menstrual cycle might indicate a successful transplant. Further investigations are needed to achieve successful clinical outcomes.

Effect of sequential cleavage and blastocyst embryo transfer compared to single cleavage stage embryo transfer on assisted reproductive technology outcome: An RCT.

Background: Assisted reproductive technology (ART), offers hope for many infertile couples by increasing the chance of successful pregnancy. The success of in vitro fertilization depends on various factors, in which embryo transfer (ET) is one of the critical steps influencing in vitro fertilization success rates. Extended embryo culture and blastocyst-stage ET have been considered in ART due to their potential benefits including improved implantation rates. Objective: This study aimed to compare the outcomes of sequential ET vs single cleavage-stage ET in women undergoing a fresh ET cycle with a limited number of embryos. Materials and Methods: This randomized clinical trial was conducted on 140 women undergoing infertility treatments and candidates for fresh ET at the Research and Clinical Center for Infertility, Yazd, Iran from August 2023 to January 2024. Women with a number of embryos from 2-5 ( ≥ 2 and ≤ 5 available embryos) were randomly divided into 2 groups: One group underwent sequential ET (one cleavage-stage ET followed by one blastocyst ET) and the other group underwent single-step 2 cleavage-stage ET. The primary outcome was clinical pregnancy, and the secondary outcome included chemical pregnancy and early abortion rates. Results: Our findings showed significantly higher rates of clinical (33.5% vs 13.6%, p = 0.003) and chemical (41.3% vs 18.2%, p = 0.004) pregnancies in the sequential ET group compared to the single-step cleavage ET group. The early abortion rate was higher in single-step cleavage ET (13% vs 44.4%, p = 0.053). Conclusion: Sequential fresh ET is a useful choice in women who have a limited number of embryos and can improve ART outcomes.

The effect of vitrification on maturation and viability capacities of immature human oocytes.

BACKGROUND: 15 % of oocytes collected from Assisted Reproductive Technology (ART) cycles are immature. These oocytes may be matured following in vitro maturation (IVM) program. It is possible to cryopreserve the immature oocytes for further use in ART after application of IVM. OBJECTIVE: The aim was to determine the maturation rate and viability of human oocytes that were matured in vitro after vitrification program. MATERIALS AND METHODS: 63 women (19-43 years old) who underwent controlled ovarian stimulation for ART were included in this study. 53 immature oocytes were used for fresh group (fIVM) and 50 immature oocytes for vitrification group (vIVM). The maturation medium was Ham's F10 supplemented with 0.75 IU FSH, 0.75 IU LH and 40 % human follicular fluid (HFF). After 36 h, maturation and morphology of all oocytes were assessed. Also, the oocyte viability was assessed using PI/Hoechst immunostaining technique. RESULTS: The maturation rates were reduced in vIVM group (56.0 %) in comparison to fIVM group (88.7 %; P < 0.001). Oocyte viability rate were also reduced in vIVM group (56.0 %) in comparison to fIVM (86.8 %, P < 0.007). CONCLUSIONS: Cryopreservation via vitrification reduced both the maturation capacity and viability of human oocytes in IVM technology. It is, therefore, recommended to apply IVM on fresh immature oocytes, instead.

Adjuvant growth hormone therapy in antagonist protocol in poor responders undergoing assisted reproductive technology.

PURPOSE: The incidence of poor ovarian response in controlled ovarian stimulation (COH) has been reported in 9-24 % of IVF-ET cycles. Growth hormone augments the effect of gonadotropin on granulosa and theca cells, and plays an essential role in ovarian function, including follicular development, estrogen synthesis and oocyte maturation. The aim of this study was to assess IVF-ET cycle outcome after the addition of growth hormone in antagonist protocol in poor responders. MATERIALS AND METHODS: Eighty-two poor responder patients selected for ART enrolled the study and were randomly divided into two groups. Group I (GH/HMG/GnRHant group, n = 40) received growth hormone/gonadotropin/GnRH antagonist protocol and group II (HMG/GnRHant group, n = 42) received gonadotropin/GnRH antagonist protocol. RESULTS: The number of retrieved oocytes was significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 6.10 ± 2.90 vs. 4.80 ± 2.40 (p = 0.035) and the number of obtained embryos was also significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 3.7 ± 2.89 as compared to 2.7 ± 1.29 (p = 0.018). There were no significant differences between groups regarding implantation, and chemical and clinical pregnancy rates. CONCLUSION: Our study showed that co-treatment with growth hormone in antagonist protocol in patients with a history of poor response in previous IVF-ET cycles did not increase pregnancy rates.

Uterine artery Doppler and endometrial blood flow in frozen embryo transfer: A cohort study.

Background: The implantation rate after assisted reproductive technology depends on 2 important factors, good quality embryo and endometrial receptivity. Endometrial receptivity is mainly assessed by ultrasound measurement of endometrial thickness and morphology. Objective: This study aimed to investigate the relationship between uterine artery Doppler indices/endometrial perfusion and pregnancy rate. Materials and Methods: This cohort study was done on 250 women who were candidates for frozen embryo transfer from January to July 2022. For assessing endometrial receptivity, we performed a Doppler ultrasound of the uterus before embryo transfer with apparently desirable endometrium (endometrial thickness ≥ 7 mm and 3 line endometrial pattern). In addition, the women were divided into 2 groups according to assisted reproductive technology outcome (clinical pregnancy), group I positive clinical pregnancy, and group II negative clinical pregnancy, and uterine artery indices and endometrial perfusion were compared between these groups. Results: Uterine artery Doppler showed that the pulsatility index was significantly different between positive and negative clinical pregnancy groups, but resistance index and peak systolic velocity (PSV) did not have statistically significant differences. Also, endometrial perfusion was significantly different between the 2 groups of clinical pregnancy. Endometrial perfusion was significantly better in positive clinical pregnancy groups. Conclusion: Doppler ultrasound can help to assess endometrial receptivity.

Comparison of Doppler ultrasound indices of uterine artery and sub endometrial blood supply in frozen embryo transfer with and without repeated implantation failure: A cross-sectional study.

Background: Uterine blood supply has been identified as a potential factor in implantation failure. Objective: This study aimed to investigate Doppler indices in the uterine artery, including vascular flow and resistance, as well as the amount of sub-endometrial blood supply in women with a history of repeated implantation failure (RIF) compared to the non-RIF group. Materials and Methods: This cross-sectional study was conducted with 139 women candidates for frozen embryo transfer in Yazd Reproductive Sciences Institute, Yazd, Iran from February to July 2023. Group A (n = 68) included women with a history of more than 2 RIF, and group B (n = 71) included women candidates for implantation for the first time without RIF. Doppler ultrasound indices of uterine artery and sub-endometrium, including sub-endometrial flow, uterine artery flow, uterine artery resistance, and peak systolic velocity, were recorded. Results: No significant differences were observed in uterine artery Doppler pulsatility index and peak systolic velocity between groups, but the uterine artery resistance index was significantly higher in the A group (p < 0.001). A significant difference was observed in the perfusion area between groups. 60/68 women in the group A had endometrial perfusion in areas 2 and 3 (p < 0.001). Conclusion: Our study revealed that women with RIF exhibited higher resistance index in sub-endometrial arteries compared to the non-RIF group.

Letrozole and ovarian hyperstimulation syndrome: Retrospective cross-sectional study.

Background: Recently, letrozole has been used to prevent moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology cycles due to its estrogen-reducing and androgen-increasing effects on the ovaries, affecting granulosa cells, and reducing vascular endothelial growth factor production. Objective: This study aimed to investigate the impact of letrozole consumption in preventing OHSS in infertile women with polycystic ovarian syndrome undergoing in vitro fertilization. Materials and Methods: In this cross-sectional study, among 1743 medical records of infertile women who were scheduled for oocyte retrieval at Research and Clinical Center for Infertility, Yazd, Iran. Data of 343 women with polycystic ovarian syndrome diagnosis and at risk of OHSS was extracted from March 2022-2023. The stimulation was carried out using a flexible gonadotropin releasing hormone (GnRH) antagonist protocol. Women were divided into 2 groups based on whether they received letrozole or not. In the letrozole group, 2.5 mg letrozole twice daily was continued from the trigger day, while in the control group, women did not receive letrozole. The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription were analyzed. Results: 89 women in the letrozole and 254 women in the control group were examined. There was no statistically significant difference between groups in terms of age and body mass index; however, anti-Mullerian hormone was significantly higher than control group (7.53 ± 4.61 vs. 5.47 ± 3.63, p < 0.001). The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription showed no significant differences between the groups. Conclusion: Recent study indicates that incorporating letrozole into the treatment of GnRH antagonists and cabergoline does not reduce the OHSS severity.

Efficacy of low-dose hCG in late follicular phase in controlled ovarian stimulation using GnRH agonist protocol.

OBJECTIVE: Safe, simple and cost-effective protocol is an important goal in ART cycles. The aim of this prospective study was whether administration of low-dose hCG in late follicular phase can be used clinically to replace gonadotropin administration in GnRH long protocol. MATERIALS AND METHODS: 122 patients who were candidates for ART enrolled the study and randomly divided into two groups. The control group (n = 62) received standard long protocol and gonadotropin administration continued until the day of hCG injection (10,000 IU) for final follicular maturation. The study group (n = 60) received GnRH long protocol and when at least ≥6 follicles with mean diameter ≥12 mm were observed in both ovaries, hMG was displaced by 200 IU per day of hCG until final follicular maturation. RESULTS: There were no significant differences in age, basal FSH, infertility duration and infertility etiology between two groups. There were no statistically significant differences between two groups regarding chemical pregnancy, clinical pregnancy, ongoing pregnancy, and abortion per cycle (50, 40, 40, and 20 % in study group vs. 45.2, 35.5, 35.5, and 21.4 % in control group, respectively). Mean dose of used gonadotropins was significantly higher in control group than that in the study group (2,524 ± 893 IU in control group and 1,439 ± 433 IU in study group) (p = 0.000). CONCLUSION: According to our data, we recommend the use of low-dose hCG in GnRH long protocol because of lower doses of used gonadotropins.

Transfer of blastocysts derived from frozen-thawed cleavage stage embryos improved ongoing pregnancy.

PURPOSE: The aim of our study was to compare the transfer of embryos that are cryopreserved in cleavage stage after thawing with the transfer of embryos after thawing and culture in sequential media until blastocyst formation. METHODS: In this prospective clinical study, we have evaluated 134 cycles of ART treatment for infertility. Frozen embryos were thawed and then cultured in sequential media until blastocyst stage in blastocyst group and were compared with thawed embryos in cleavage stage group. RESULTS: Implantation rate was significantly higher in blastocyst group (30 %) compared to cleavage group (17 %). No statistical differences were reported in chemical and clinical pregnancy rates between groups. Ongoing pregnancy rate was significantly higher in blastocyst group compared to cleavage group (42.9 vs. 24.6 %). CONCLUSIONS: Our results indicated that blastocyst formation after thawing of cleavage stage embryos is a good predictor for embryo viability and pregnancy outcome.

Correction to "Effect of granulocyte colony stimulating factor (G-CSF) on IVF outcomes in infertile women: An RCT" [Int J Reprod BioMed 2016; 14: 341-346].

[This corrects the article on p. 341 in vol. 14 PMCPMC4910038.].

Correction to "Effect of vitamin D insufficiency treatment on fertility outcomes in frozen-thawed embryo transfer cycles: A randomized clinical trial" [Iran J Reprod Med 2014; 12: 595-600].

[This corrects the article on p. 595 in vol. 12 PMCPMC4248143.].

Corrigendum to "Correlation between clinical and laboratory parameters and early pregnancy loss in assisted reproductive technology cycles: A cross-sectional study" [Int J Reprod BioMed 2022; 20: 683-690].

[This corrects the article DOI: 10.18502/ijrm.v20i8.11757.].

Correlation between clinical and laboratory parameters and early pregnancy loss in assisted reproductive technology cycles: A cross-sectional study.

Background: The miscarriage rate after pregnancy resulting from assisted reproductive technology (ART) is about 20%, roughly half of which is biochemical. The correlations between the number and quality of oocytes, estradiol level and early pregnancy loss have not been fully clarified. Objective: This study aimed to examine the clinical and laboratory parameter effects on early abortion in ART cycles. Materials and Methods: In this cross-sectional study, 408 women who were ART candidates and were referred to the Yazd Infertility and Research Center, Yazd, Iran during March 2017 to March 2020 participated. Women who had a fresh embryo transferred and who had a positive beta human chorionic gonadotropin serum test were included in the study. The Anti-Müllerian hormone (AMH) level, embryo quality, oocyte number, progesterone level, estradiol level, and maternal age were extracted from the medical records. Results: No significant difference was observed in the age, mean estradiol and progesterone levels on trigger day, number of MII oocytes, and embryo quality between the groups (p = 0.19, 0.42, 0.07, 0.34 and 0.20, respectively). No statistically significant difference was found between the 3 groups of AMH level (p = 0.20). After evaluation using logistic regression, the rate of negative clinical pregnancies was higher in the group with AMH < 1 ng/ml. However, this was not found to be statistically significant. Conclusion: We did not find any correlation between early abortion and AMH levels, embryo quality, oocyte number, progesterone level, estradiol level, or maternal age.