Controlled ovarian stimulation in cancer patients under 18 years old; a case series.

BACKGROUND: Fertility preservation for adolescent pubescent girls is a concern of the healthcare system and parents. Oocyte cryopreservation is regarded as a standard medical intervention for patients with a minimum age of 18 years. Evidence suggests that mature oocyte cryopreservation is possible for adolescent pubescent girls, although, ovarian stimulation for these patients remains a challenge. CASES PRESENTATION: This case series is the first report regarding ovarian stimulation with oocyte cryopreservation in younger than 18 years cancerous girls, who refer to ROYAN institute, Tehran, Iran, prior to the start of the treatment of cancer (November 2015 to February 2021). The oocyte cryopreservation was carried out in the 7 patients (five patients with Hodgkin lymphoma, one patient with Ewing sarcoma, and one patient with osteogenic tumor), the embryo cryopreservation in one patient with dysgerminoma, and the oocyte and embryo cryopreservation in one patient with germ cell tumor. No oocytes were retrieved after ovarian stimulation in the patient with medulloblastoma. For one of the patients with Hodgkin lymphoma, half of the tissues of one ovary were cryopreserved prior to ovarian stimulation. CONCLUSIONS: Oocyte cryopreservation is a feasible option of fertility preservation in the adolescent's patients with cancer. However, only if reported acceptable fertilization rates, as well as the successful cases of live birth from oocyte cryopreservation at the ages under 18, this option of preserving fertility can be applied to this age range.

Does The Culture of Post-Thawed Cleavage-Stage Embryos to Blastocysts Improve Infertility Treatment Outcomes of Frozen-Thawed Embryo Transfer Cycles? A Randomised Clinical Trial.

BACKGROUND: There is a definite shift in assisted reproductive centres from cleavage-stage embryo transfer (ET) to blastocyst transfer that is attributed to improvements in laboratory environments and advances in the development of embryo culture media. The aim of the study was to investigate the reproductive outcomes of thawed cleavage-stage ET versus blastocysts derived from an extended culture of these embryos. MATERIALS AND METHODS: This open-label, randomised, parallel group clinical trial study enrolled 182 women aged ≤37 years who underwent frozen-thawed ET from November 2015 to June 2020 at Royan Institute Research Centre, Tehran, Iran. The women were randomly assigned to either the thawed cleavage ET group (n=110) or the post-thaw extended culture blastocysts group (n=72). The primary outcome measure was the clinical pregnancy rate. Secondary outcome measures were implantation rate, live birth rate (LBR), and miscarriage rate. A P<0.05 indicated statistical significance. RESULTS: There were no significant differences between the two groups in terms of demographic characteristics. Both the mean numbers of embryos transferred and good quality embryos transferred were significantly lower in the postthaw extended culture blastocysts group compared to thawed cleavage-stage ET cycles. However, the post-thaw extended culture blastocysts group had higher clinical pregnancy (56.94 vs. 40.91%, P=0.034), implantation (34.43 vs. 19.84%, P=0.001) and live birth (49.3 vs. 33.63%, P=0.036) rates compared to the thawed cleavage-stage ET group. Miscarriage and multiple gestations rates were comparable between the groups. CONCLUSION: These results allow us to take a position in favour of post-thaw extended culture blastocysts; thus, it is important to improve the post-thawing extended culture technique (registration number: NCT02681029).

Royan Institute First Attempts: Autotransplantation of Vitrified Human Ovarian Tissue in Cancer Patients.

Today, timely diagnosis and therapeutic progress open a road of hope for survival in cancerous patients. Increased knowledge about the various cytotoxic treatment's impacts on ovarian function and fertility has resulted in a surge in the number of patients seeking to preserve their fertility before starting the anti-cancer treatment process. In this regard, embryo cryopreservation can be recommended for fertility preservation when the woman is married and has adequate time for ovarian stimulation. If patients are prepubertal girls or not married women, oocytes or ovarian tissue can be frozen instead to be used in the future. In this regard, the first attempts for ovarian tissue transplantations were conducted in 2016 and in 2019 for two cancerous patients whose ovarian tissue was cryopreserved in the Royan Human Ovarian Tissue Bank (Tehran, Iran). Unfortunately, the transplantations did not result in a live birth.

Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial.

BACKGROUND: Currently, optimal method of ovarian stimulation (OS) to in-vitro fertilization (IVF) in the patients with polycystic ovarian syndrome (PCOS) is unknown. The present research aims to study the efficiency of minimal-OS method in treatment of infertile patients with PCOS and also the effect of gonadotropin type (recombinant FSH (r-FSH) vs. urinary Human menopausal gonadotropin (u-HMG)) on treatment cycles with GnRH-antagonist. METHODS: In this randomized controlled trial, a total of 120 eligible patients were randomly allocated into four groups of OS to IVF: minimal-OS with r-FSH, minimal-OS with u-HMG, mild-OS with r-FSH and mild-OS with u-HMG. IVF outcomes of groups were analyzed statically. RESULTS: The statistical analysis showed that there were significant differences among groups regarding stimulation duration (p < 0.0001), number of retrieved oocytes (p < 0.0001), number of obtained embryos (p < 0.0001). There were no statistically significant differences in fertilization rate (p = 0.289) and implantation rate (p = 0.757) among our participants. There were also significant differences among these four groups in terms of clinical pregnancy rate (/ET and /cycles) (p < 0.0001, p = 0.021, respectively) and live birth rate/cycles (p < 0.0001). Also cases of freeze all embryos due to prevention of ovarian hyper stimulation syndrome (OHSS) (p = 0.004). CONCLUSIONS: On the basis of present results the minimal-OS with u-HMG may be one of optimal methods of control OS in the patients with PCOS in respect to serum levels of estradiol on the day of triggering final oocyte maturation, total dose of prescribed gonadotropin, the optimal number of oocytes and embryos obtained, rate of clinical pregnancy and the incidence of OHSS risk. TRIAL REGISTRATION: NCT, NCT03876145. Registered 15/03/2019. Retrospectively registered, http://www. CLINICALTRIAL: gov/ NCT03876145.

Evaluation of the relationship between ovarian reserve with congenital anomalies and intramural uterine leiomyoma among infertile women: a cross-sectional study.

BACKGROUND: Ovarian reserve is a crucial indicator of a woman's fertility potential, which is determined by the quality and quantity of antral follicles and oocytes. However, certain factors such as endometriosis, pelvic inflammatory disease, myoma, and the natural process of aging can lead to a poor ovarian response to stimulation, reducing a woman's chances of conceiving. OBJECTIVE: To evaluate the effect of uterus congenital anomalies and uterine leiomyoma are associated on ovarian reserve. METHODS: The present cross-sectional study was performed on 321 infertile women in three groups consisted of 97 infertile women with intramural uterine leiomyoma and 81 infertile women with uterine anomalies and 143 infertile women without uterine anomalies and uterine leiomyoma during 2017-2019 in Royan Center. Sampling method was continuous and available. Data collection tool in this study was a questionnaire which was in two parts of individual variables and the second part was related to ultrasound results (number of antral follicles and ovarian volume) and laboratory tests (Anti-Mullerian Hormone (AMH) and Follicle-stimulating Hormone (FSH)). Ovarian reserve parameters were measured in three groups on the third day of the cycle in both groups. Data analysis was performed using SPSS software version 21. Quantitative variables were analyzed using t-test, qualitative variables were analyzed using chi-square test. RESULTS: The results of in laboratory parameters showed that there was no statistically significant difference between the three groups in FSH (2.35 ± 1.55, 2.07 ± 1.81, 2.31 ± 1.93) and AMH (6.84 ± 2.75,7.52 ± 3.14,6.93 ± 3.04), respectively (P > 0.05). The results of sonographic variables also showed that the variables include number of antral follicles in right ovarian, number of antral follicles in left ovarian have statistically significant between the three groups (5.73 ± 2.69,4.84 ± 3.14,6.66 ± 3.13), respectively (P < 0.05). CONCLUSION: The results of the present study showed that uterine abnormalities and uterine leiomyoma with different mechanisms such as reduce of antral follicle numbers and the effect on uterine and ovarian blood flow lead to a decrease in ovarian reserve and infertility. Therefore, treatment and surgery can reduce these effects and improve the fertility of the affected women.

Differential expression of innate/adaptive immunity genes induced by endometrial scratching as a hopeful approach for implantation boosting in unexplained, repeated implantation failure: An RCT.

BACKGROUND: Endometrial scratching (ES) has been proposed as a potential treatment for implantation improvement in unexplained repeated implantation failure (uRIF) patients, however, little is known about its exact molecular mechanisms. OBJECTIVE: This randomized controlled trial (RCT) was conducted on twenty uRIF patients to investigate the expression of innate and adaptive immune signaling genes after ES. METHODS: Ten uRIF patients in the intervention (twice endometrial sampling in follicular and luteal phases) and 10 uRIF patients in the control group (only luteal phase sampling) were randomly enrolled. Gene expression analysis with innate and adaptive immune response PCR-array kit between intervention and control groups were performed. RESULTS: Among innate immune-associated genes, a significant decrease was observed in the expression of APCS, CPR, CCL2, NLRP3, HLA-A, TLR3 and TLR4 in the intervention group. In adaptive immune-related genes, the expression level of CD80, CD86, CXCR3, IFNγ, IFNα1, IFNß, MBL2, CCR6, CCR8 and IL17A were decreased and CSF2, GATA3, and IL4 increased significantly in the intervention group (P < 0.05). Of 14 uRIF patients, five live birth (35.71 %) was achieved. CONCLUSION: ES in uRIF patients may exert positive effects on the endometrial preparation which increases its receptivity for embryo implantation by modulating the expression of an array of immune signaling pathway genes.

Endometrial preparation for vitrified-warmed embryo transfer with or without GnRH-agonist pre-treatment in patients with polycystic ovary syndrome: a randomized controlled trial.

RESEARCH QUESTION: What are the effects on pregnancy outcome in patients with polycystic ovary syndrome (PCOS) in endometrial preparation cycles for vitrified-warmed embryo transfer with or without gonadotrophin releasing hormone (GnRH) agonist pre-treatment? DESIGN: A total of 212 patients with PCOS referred to Royan Institute, Tehran, Iran, between 20 August 2017 to 20 June 2018 were included. The patients were randomly assigned to receive oestradiol after downregulation with GnRH agonist (group A) or without GnRH agonist down-regulation (group B). RESULTS: A total of 188 patients with PCOS completed the trial, 93 patients in group A and 95 patients in group B. Basal oestradiol and LH levels were significantly higher in group B (26.66 versus 41.61, P = 0.01 and 0.93 versus 5.33, P < 0.0001, respectively). Clinical pregnancy rates were not significantly different in both groups (31.2% versus 33.7%). Similarly, no significant differences were found between groups A and B in miscarriage (9.7% versus 11.6%), implantation (0.58 versus 0.51) and live birth (21.7% versus 22.1%) rates and for medical complications during pregnancy and neonatal anomalies. CONCLUSIONS: Our findings indicate that endometrial preparation for frozen-thawed embryo transfer with and without ovarian suppression by GnRH agonist provides similar results.

Live birth rates after different endometrial preparation methods in frozen cleavage-stage embryo transfer cycles: a randomized controlled trial.

PURPOSE: This study aimed to compare the clinical outcomes in different endometrial preparation methods prior to frozen embryo transfer (FET) in women with normal menstrual cycles. METHODS: A total of 471 eligible patients were randomly allocated into four groups of endometrial preparation prior to FET: natural cycle with spontaneous ovulation (n = 120), natural cycle with human chorionic gonadotropin (hCG) for ovulation induction (n = 117), hormone replacement cycle (HRC) (n = 113) and HRC with pre-treatment with GnRH-a (n = 121). Natural cycle with hCG also received hCG in luteal phase. The primary outcome was live birth rate. The secondary outcomes included implantation, biochemical and clinical pregnancy, ongoing pregnancy, and late miscarriage rates. Data analysis included t test, ANOVA and χ2. RESULTS: There were no statistically significant differences in the mean age (p = 0.31), duration (p = 0.43) and cause of infertility (p = 0.77) and the number (p = 0.33) and quality (p = 0.21) of embryos transferred between the groups. No significant differences regarding the implantation rates per embryo transfer (p = 0.97) and biochemical pregnancy rates (p = 0.90) were observed between the groups. The rates of clinical pregnancy were 34.2%, 32.5%, 31% and 36.4% in the natural cycle, natural with hCG, HRC and HRC with GnRH-a groups, respectively (p = 0.83). Ongoing pregnancy (p = 0.89) and miscarriage (p = 0.33) rates were comparable between groups. The rate of live birth was 30.8% in the natural group, 30% in the natural with hCG, 27.4% in the HRC and 31.4% in the HRC with GnRH-a groups (p = 0.91). CONCLUSION: Four different types of endometrial preparation methods for FET cycles appear to be equally effective in terms of implantation, pregnancy, miscarriage and live birth rates in women with normal menstrual cycles. CLINICAL TRIAL REGISTRATION NUMBER: NCT02251925.

Does the "delayed start" protocol with gonadotropin-releasing hormone antagonist improve the pregnancy outcome in Bologna poor responders? a randomized clinical trial.

BACKGROUND: Recently, a novel approach with delaying the start of controlled ovarian stimulation along with gonadotropin-releasing hormone (GnRH) antagonist pretreatment for 7 days after estrogen priming for further suppression of endogenous follicle stimulating hormone (FSH) during the early follicular phase, resulting in more FSH-responsive follicles and thus improving synchronous follicular development was introduced. Two clinical trials have examined this strategy and reported controversial results. This study aimed to compare the effect of delayed-start GnRH antagonist protocol and standard GnRH antagonist in patients with poor ovarian response (POR) undergoing in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI). METHODS: This randomized clinical trial was conducted at infertility department of Royan Institute from January 2017 to June 2018. Poor ovarian response was defined according to the Bologna criteria. The eligible women were randomly allocated into an experimental and control groups. In experimental group, patients received delayed-start GnRH antagonist protocol with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin and in control group, patients treated with estrogen priming antagonist protocol. IVF/ICSI outcomes were compared between groups. RESULTS: Among all the 250 patients examined 156 women were eligible for study and finally 120 patients were allocated to intervention (n = 60) and control (n = 60) groups. Demographic characteristics and hormonal profiles of the patients did not differ between groups. The statistical analysis showed that there were significant differences between groups regarding the total dose of used gonadotropins (P < 0.001), stimulation duration (P < 0.001), number of retrieved oocytes (P = 0.01) and top quality embryo (P < 0.001) and also cancellation (P = 0.002) and fertilization rates (P = 0.002). CONCLUSION: On the basis of present results the delayed-start protocol in poor responders can improve the fertilization rate and quality of embryos and reduce the cycle cancellation but have no significant effect on clinical pregnancy rate; however, larger randomized clinical trials are required to compare it with other protocols. TRIAL REGISTRATION: NCT, NCT03134690. Registered 1 May 2017 - Retrospectively registered, http://www.clinicaltrial.gov / NCT03134690.