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. Increasedknowledge about the various cytotoxic treatment's impacts on ovarian function and fertility has resulted in a surgein the number of patients seeking to preserve their fertility before starting the anti-cancer treatment process. In thisregard, embryo cryopreservation can be recommended for fertility preservation when the woman is married and hasadequate time for ovarian stimulation. If patients are prepubertal girls or not married women, oocytes or ovarian tissuecan be frozen instead to be used in the future. In this regard, the first attempts for ovarian tissue transplantations wereconducted in 2016 and in 2019 for two cancerous patients whose ovarian tissue was cryopreserved in the RoyanHuman Ovarian Tissue Bank (Tehran, Iran). Unfortunately, the transplantations did not result in a live birth

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

Abstract 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

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

Abstract 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

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

Abstract 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

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) toblastocyst transfer that is attributed to improvements in laboratory environments and advances in the development ofembryo culture media. The aim of the study was to investigate the reproductive outcomes of thawed cleavage-stage ET versusblastocysts derived from an extended culture of these embryos.Materials and Methods: This open-label, randomised, parallel group clinical trial study enrolled 182 women aged ≤37years 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 cultureblastocysts group (n=72). The primary outcome measure was the clinical pregnancy rate. Secondary outcome measureswere 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. Boththe mean numbers of embryos transferred and good quality embryos transferred were significantly lower in the post-thawextended culture blastocysts group compared to thawed cleavage-stage ET cycles. However, the post-thaw extendedculture 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 isimportant to improve the post-thawing extended culture technique (registration number: NCT02681029)

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

Abstract 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