Cryopreserved Embryo Transfer Research Articles

Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy. POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months. Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5). In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.

Abstract GS02-11: Fertility preservation and assisted reproductive technologies (ART) in breast cancer (BC) patients (pts) interrupting endocrine therapy (ET) to attempt pregnancy

Abstract Background: The POSITIVE trial recently demonstrated that temporary interruption of ET to attempt pregnancy does not increase the short-term risk of recurrence in pts with hormone receptor-positive (HR+) BC. Yet, uncertainty exists regarding the safety of ovarian stimulation for embryo/oocyte cryopreservation to preserve fertility in these pts. In addition, very limited data exist regarding safety and efficiency of ART to achieve pregnancy after ET interruption. Methods: POSITIVE is an international, single-arm, prospective trial that enrolled pts ≤ 42 years with stage I-III HR+ BC who had already received 18-30 months of ET prior to enrollment. The use of ART was a predefined 2ry endpoint. We evaluated factors associated with time to pregnancy in a Fine and Gray competing risks model, which included chemotherapy (chemo) ± GnRH analogue (GnRHa), age, prior ET, prior birth, and menstrual status at enrollment. The cumulative incidence of pregnancy at 12 months from enrollment by age was estimated controlling for competing risks. We performed a logistic regression model to evaluate whether ART use was associated with achieving pregnancy, adjusting for age, receipt of chemo ± GnRHa. The cumulative incidence of BCFI events was estimated according to whether or not ovarian stimulation for cryopreservation was performed at diagnosis and prior to enrollment. BC-free interval (BCFI) was defined as the time from enrollment until the first BC event (invasive local, regional, or distant recurrence or contralateral disease). A 24-month landmark analysis was performed to investigate the safety of ART use after enrollment. Median follow-up was 41 months. Results: 497 out of 516 included pts (96%) were followed for at least 6 months and were evaluable for pregnancy status. 368 out of 497 evaluable pts (74%) reported at least one pregnancy. In a multivariable model, young age was the only factor associated with shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64%, 54% and 38% for pts aged &amp;lt; 35, 35-39 and 40-42 years, respectively. 179 pts (36.0%) had undergone ovarian stimulation for embryo/oocyte cryopreservation at diagnosis and prior to enrollment, of whom 68 (37.9%) reported cryopreserved embryo transfer after enrollment. 215 pts (43.3%) reported using any ART after enrollment, of whom 80 (37.2%) underwent ovarian stimulation for in-vitro fertilization (FIVET) or intracytoplasmic sperm injection (ICSI). Other ART used included clomiphene (n=19), intrauterine insemination (n=37) and egg donation (n=17). Pregnancy rates were 82.4% and 67.5% for women who underwent cryopreserved embryo transfer and FIVET/ICSI, respectively. In a multivariate model, cryopreserved embryo transfer was the only ART independently associated with a higher chance of pregnancy (OR:2.41, 95% CI: 1.75-4.95). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis and before enrollment, 9.7% (95% CI: 6.0-15.4%), and those who did not, 8.7% (95% CI: 6.0-12.5%). A 24-month landmark analysis showed no impact of ovarian stimulation for FIVET/ICSI after enrollment on BCFI. Conclusions: This is the largest prospective study to investigate fertility preservation and ART in pts with HR+ BC. Young age was the main factor associated with shorter time to pregnancy. Embryo/oocyte cryopreservation at BC diagnosis followed by embryo transfer after ET interruption was the only approach associated with an increased chance of pregnancy. Ovarian stimulation either at BC diagnosis for embryo/oocyte cryopreservation or after enrollment to POSITIVE for FIVET/ICSI did not appear to impact prognosis in the short term. These data are of paramount importance for oncofertility counselling of young BC pts. Citation Format: Hatem Azim, Samuel Niman, Ann Partridge, Isabelle Demeestere, Monica Ruggeri, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna Saetersdal, Judith Kroep, Audrey Mailliez, Ellen Warner, Virginia Borges, Frédéric Amant, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Junko Takei, Jeong Eon Lee, Janice Walshe, Manuel Ruíz - Borrego, Halle Moore, Christobel Saunders, Vesna Bjelic-Radisic, Snezana Susnjar, Fatima Cardoso, Natalie Klar, Tanya Spanic, Kathryn Ruddy, Martine Piccart, Larissa Korde, Aron Goldhirsch, Richard Gelber, Olivia Pagani, Fedro Alessandro Peccatori. Fertility preservation and assisted reproductive technologies (ART) in breast cancer (BC) patients (pts) interrupting endocrine therapy (ET) to attempt pregnancy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-11.

Regulation of Assisted Reproduction in Hungary

Following the implementation of state oversight of human reproductive procedures in 2020, several regulations have been introduced to mitigate potential issues. To enhance patient care and alleviate the workload of IVF centers, a network of specialized infertility outpatient clinics will be established alongside existing centers of assisted reproduction. These changes aim to address the challenges faced by infertility centers and improve the chances of patients having children. The policy currently allows for up to five insurance-funded treatment cycles, while cryopreserved embryo transfers are not subject to a specific limit. Furthermore, the previous threemonth waiting period between treatment cycles has been eliminated, and restrictions on the number of embryos that can be implanted have been implemented. Limiting the number of embryos transferred during IVF procedures is a common practice aimed at reducing the risks associated with multiple pregnancies. By allowing only one embryo for the first transfer up to the age of 36, especially when transferred on day five of embryonic development, this initiative prioritizes the health and safety of both the mother and potential offspring. It helps to minimize the chances of complications such as preterm birth and low birth weight, which are more common with multiple pregnancies. Additionally, it can improve the overall success rates of IVF by focusing on the quality of the transferred embryo rather than the quantity. The Hungarian government anticipates that these measures will enhance the success rates of IVF treatments, consequently leading to a rise in future childbirths and a decrease in the number of frozen embryos. This study aims to delineate the effectiveness of the introduced changes in 2023 and provide recommendations accordingly.

The use of an embryo transfer simulator to compare transfer techniques and pregnancy outcomes among physicians

To evaluate the association between embryo transfer techniques and pregnancy outcomes. This is a prospective observational study with a retrospective cohort. University Clinic. Patients underwent embryo transfers between 2015 and2020. Fourteen physicians performed 25 mock embryo transfers on the embryo transfer simulator and completed a questionnaire assessing preferred embryo transfer techniques. Quantitative performance metrics on the embryo transfer simulator were measured. Individual physician embryo transfer success rates were retrospectively collected from all fresh and cryopreserved embryo transfers between January 1, 2015, and January 1, 2020. Associations between embryo transfer techniques (preferred technique and simulator performance metrics) and each physician's historical patient pregnancy outcomes were assessed. Associations between embryo transfer techniques and live births were assessed. There were significant differences in embryo transfer techniques between physicians, including touches to the fundus, distance to the fundus, duration of embryo transfer, duration of the complete procedure, time spent navigating the cervical canal, velocity of embryo expulsion, time waited after embryo expulsion, and total score on the embryo transfer simulator. After controlling for confounders and multiple transfers per physician, the duration of embryo transfer was significantly associated with live birth, with longer durations associated with decreased live birth rates. Shorter placement distance to the fundus and higher velocity of embryo expulsion were both significantly associated with higher rates of ectopic pregnancy. This study revealed significant differences in transfer techniques among physicians. The use of the embryo transfer simulator for physicians in practice can elucidate differences and create opportunities for data-driven improvement in embryo transfer success rates.

Laser assisted thinning versus drilling in cryopreserved embryo transfer cycles

Laser assisted thinning versus drilling in cryopreserved embryo transfer cycles

Asszisztált reprodukció újragondolva

Following the implementation of state oversight of human reproductive procedures in 2020, several regulations have been introduced to mitigate potential issues. To enhance patient care and alleviate the workload of IVF centres, a network of specialized infertility outpatient clinics will be established alongside existing centres of assisted reproduction. These changes aim to address the challenges faced by infertility centres and improve the chances of patients having children. The policy currently allows for up to five insurance-funded treatment cycles, while cryopreserved embryo transfers are not subject to a specific limit. Furthermore, the previous three-month waiting period between treatment cycles has been eliminated, and restrictions on the number of embryos that can be implanted have been implemented. Limiting the number of embryos transferred during IVF procedures is a common practice aimed at reducing the risks associated with multiple pregnancies. By allowing only one embryo for the first transfer up to the age of 36, especially when transferred on day five of embryonic development, this initiative prioritizes the health and safety of both the mother and potential offspring. It helps to minimize the chances of complications such as preterm birth and low birth weight, which are more common with multiple pregnancies. Additionally, it can improve the overall success rates of IVF by focusing on the quality of the transferred embryo rather than the quantity. The Hungarian government anticipates that these measures will enhance the success rates of IVF treatments, consequently leading to a rise in future childbirths and a decrease in the number of frozen embryos. This study aims to delineate the effectiveness of the introduced changes in 2023 and provide recommendations accordingly.

Association of duration of embryo culture with risk of large for gestational age delivery in cryopreserved embryo transfer cycles

To examine the relationship between the day of embryo cryopreservation and large for gestational age (LGA) infants in women undergoing frozen embryo transfers (FETs) after cryopreservation on days 2-7 after fertilization and to compare the risk of the day of embryo cryopreservation to other possible risk factors of LGA after FET cycles. Retrospective cohort study. Society of Assisted Reproduction Clinical Outcomes Reporting System. Women undergoing FET cycles. Day of cryopreservation. Singleton LGA infant. A total of 33,030 (18.2%) FET cycles in the study group (n = 181,592) resulted in LGA infants during the study period of 2014-2019. There was an increase in LGA risk when cryopreservation was performed from day 2 (13.7%) to days 3-7 (14.4%, 15.0%, 18.2%, 18.5%, and 18.9%). In the log-binomial model, the risk increased compared with days 2-3 combined when cryopreservation was performed on days 5-7 (adjusted relative risk [aRR] 1.32, 95% confidence interval [CI] 1.22-1.44 for day 5, aRR 1.34, 95% CI 1.23-1.46 for day 6, and aRR 1.42, 95% CI 1.25-1.61 for day 7). Other factors most associated with LGA risk in the log-binomial model were preterm parity of >3 compared with 0 (aRR 1.82, 95% CI 1.24-2.69) and body mass index (BMI) of >35 kg/m2 compared with normal weight (aRR 1.94, 95% CI 1.88-2.01). Increasing gravity, parity, BMI, number of oocytes, and embryo grade were also associated with LGA in this model. Asian, Black, Hispanic, and combined Hawaiian and Pacific Islander were protective factors in the model compared with White patients. Low BMI (<18.5 kg/m2) was also considered a protective factor in the model compared with normal BMI. Duration of embryo culture was associated with an increased risk of LGA in this study cohort when controlling for known confounders such as maternal BMI and parity. This study sheds new light on the possible link between FET and LGA infants.

P-327 Intrauterine fluid in patients with cesarean section defects in association with ivf outcomes

Abstract Study question This study evaluate the effect of cesarean section scar defects associated with intrauterine fluid during endometrial preparation on pregnancy outcomes. Summary answer Patients with Cesarean section scar defect and intrauterine fluid during endometrial preparation had a substantially lower pregnancy outcome compared to those without uterine fluid. What is known already The Cesarean section rate in developed countries has increased continuously, leaving many short-term and long-term consequences. Intrauterine fluid, which reported incidence may reach 40% in patients who have had a previous caesarean section, may play an important role in reducing endometrial receptivity and further impair pregnancy outcomes. Study design, size, duration This is a retrospective cohort study performed on patients who had undergone frozen embryo transfer at an Assisted Reproductive Technology Center from January 2019 to December 2019. Participants/materials, setting, methods 2,350 patients without intrauterine fluid and 74 patients with Cesarean section scar defect who had intrauterine fluid during endometrial preparation but none at progesterone supplementation were analyzed. Multiple logistic regression was performed for the probability of the pregnancy outcome of embryo transfer and measured the association with the status of intrauterine fluid, age, endometrial thickness, number of previous transfer, number of embryos, type of infertility, and difficult embryo transfer at the alpha level of 0.05%. Main results and the role of chance The outcomes among 2,424 patients undergoing cryopreserved embryo transfer were 59.45% for pregnancy rate, 8.7% for biochemical pregnancy rate, 50.33% for clinical pregnancy rate, and 43.15% for ongoing pregnancy rate. The analysis of multiple logistic regression indicated that the presence of intrauterine fluid during endometrial preparation did not affect the pregnancy rate. However, in patients with intrauterine fluid, there was an increased rate of biochemical pregnancy (OR 2.46, 95%CI 1.35-4.50) and a reduced rate of ongoing pregnancy (OR 0.54, 95%CI 0.32-0.89). Limitations, reasons for caution The major limitations of the present study are the retrospective design and small number of patients with uterine fluid. Additionally, the composition of the uterine fluid (eg, blood, mucus, purulent, or transparent) cannot be classified by an ultrasound exam. Wider implications of the findings Intrauterine fluid may be an innovative and controllable factor that should be considered in patients who have a history of caesarean section in order to improve pregnancy outcomes. Trial registration number Not Applicable

P-693 Retrospective evaluation of the effect of the implementation of the DIVINE dose-calculator in daily practice on ovarian hyperstimulation treatment risk and live birth rate

Abstract Study question Does the implementation of the DIVINE dose-calculator in routine care decrease treatment risk due to ovarian hyperstimulation whilst maintaining treatment efficacy? Summary answer The implementation of the DIVINE dose-calculator significantly decreases treatment risks caused by ovarian hyperstimulation, without affecting treatment efficacy in terms of live birth. What is known already Meta-analyses show that tailoring the gonadotropin starting dose did not affect live birth rates, but reduced treatment risks. The ORT iOS IPD-MA study group used individual participant data to develop and validate a model for ovarian stimulation in IVF/ICSI: the DIVINE dose-calculator. This model scored adequate for assessing hyperstimulation treatment risk and poor for predicting live birth. It provides clinicians an overview of risk percentages per gonadotropin starting dose, which aids in selecting an appropriate, personalized gonadotropin starting dose. This model should be implemented in routine care to confirm the true clinical effect on treatment risk and live birth results. Study design, size, duration Retrospective cohort study using pseudonymized data in two fertility centers in The Netherlands. The dose-calculator was implemented on 15th February 2021. Data from 36 months before and 12 months after implementation were collected. The dose-calculator included female age, AMH and GnRH-type in order to select a starting dose between 100-225 IU. Baseline characteristics and fresh cycle treatment outcomes were extracted from the patient file, checked and cleaned. Missing data were imputed 50 times. Participants/materials, setting, methods Subfertile women younger than 38 years, starting their first IVF/ICSI treatment cycle with follitropin alfa or beta were included. Couples who did not plan to receive a fresh embryo transfer, women diagnosed with PCOS and couples undergoing limited insemination or PGT were excluded. Intention-to-treat and per protocol analyses were completed. Inverse propensity weighting was applied to balance confounders. Weighted regression was then performed using general linear models or ordered logistic regression models. Main results and the role of chance 493 women were included, 401 in the standard group and 92 in the dose-calculator group (per protocol analysis). There was no difference in live birth rate before and after implementation: 25.4% vs 25.0% respectively (OR: 1.01, 95% CI: 0.6 – 1.71). Ovarian hyperstimulation treatment risk clearly decreased after the implementation of the dose-calculator from 11.3% in the pre-implementation period to 4.3% in the post-implementation period (OR: 0.27, 95% CI: 0.08 – 0,91), of which OHSS incidence declined from 6.8% to 0% after implementation. Pre-implementation, women stimulated 1.0 day shorter as compared to the post-implementation period (MD, CI: 0.25 – 1.75), and used 200 IU gonadotropins less per cycle (MD, 95% CI: 48.68 – 352.11). The cancellation rate due to low ovarian response were equal pre- versus post-implementation (OR: 0.94, 95% CI: 0.45 – 1.98) as well as the cancellation rate due to high ovarian response (OR: 0.56, 95% CI: 0.11 – 2.84). Post-implementation 1.05 less oocytes were collected during follicle aspiration (MD, 95% CI: -2.51 – 0.41), which resulted in 0.41 less usable embryos (MD, 95% CI: -1.04 – 0.17). The usable embryo per oocyte was comparable (MD: 0.003, 95% CI: -0.061 – 0.067). The intention-to-treat analysis confirmed these results. Limitations, reasons for caution Results are preliminary and based on single center data. We expect to finalize the analyses including approximately 100 patients from the second center and a cost-effectiveness analysis before ESHRE 2023. Unfortunately, cumulative cycle results including cryopreserved embryo transfers and subsequent treatment cycles are not available. Wider implications of the findings The dose-calculator aids in optimizing ovarian stimulation, without compromising live birth prospects. It is an easy to use model, which substantially reduces risks caused by ovarian hyperstimulation. A free of charge mobile application will be developed to stimulate implementation. Future research should address cumulative cycle results and temporal/geographical validation. Trial registration number Not applicable

A pilot study of the intrauterine non-ablative erbium laser effectiveness in the endometrium preparation for cryopreserved embryo transfer in women with a history of implantation failures

Background. Embryo implantation failure remains an urgent issue of assisted reproductive technologies (ART).&#x0D; Aim. To determine the effect of intrauterine irradiation with a non-ablative erbium laser on the endometrium state using the histological and immunohistochemical examination and to evaluate its effectiveness in ART cryo-protocols.&#x0D; Materials and methods. The study enrolled 25 women aged 2645 with 1 to 5 failed implantations who were planning a pregnancy in a cryopreserved embryo transfer protocol. On days 610 of the menstrual cycle, all patients underwent a single procedure of intrauterine irradiation of the endometrium and cervical canal mucosa with an erbium laser in a non-ablative mode using Fotona SP Dynamis laser system (Slovenia). The histological and immunohistochemical data of the endometrium before and 12 months after the procedure and the pregnancy rate with subsequent transfer of the cryopreserved embryo were assessed.&#x0D; Results. Intrauterine irradiation with a non-ablative erbium laser increased the proliferative activity of the endometrium (p=0.029), the expression of vascular endothelial growth factor (p=0.029), reduced the sclerosis lesions in the spiral arteries and endometrial stroma, increased the expression of progesterone and estrogen receptors, thus significantly increasing the effectiveness of the ART cryo-protocols (p=0.013).

Birth of monozygotic dichorionic twins after a single blastocyst embryo transfer: a case report of genetic determination of zygosity

To report a case of monozygotic dichorionic (DC) twins after a single cryopreserved blastocyst embryo transfer followed by genetic determination of zygosity postpartum. Case report. University hospital. A 26-year-old woman with polycystic ovary syndrome and her 36-year-old male partner with severe oligozoospermia, resulting in a 1.5-year history of primary infertility. Controlled ovarian stimulation and intracytoplasmic sperm injection treatment with single cryopreserved embryo transfer at blastocyst stage. Ultrasound images of the fetuses and short tandem repeat genotyping postpartum. A DC twin pregnancy following a single cryopreserved blastocyst embryo transfer was confirmed at the first trimester screening. Confirmatory testing performed postpartum included short tandem repeat analysis determining monozygosity and pathology examination reporting DC placental configuration. Dichorionic monozygotic twins are thought to arise from the splitting of an embryo before the blastocyst stage. This case suggests that placental configuration of monozygotic twins may not strictly depend on timing of embryo division. Genetic analysis is the only tool to confirm the zygosity.

Laparoscopic embryo transfer in pigs - comparison of different variants and efficiencies of the method.

The aim of the study was to develop a method of laparoscopic embryo transfer in pigs and to compare different variants of this method. Two catheter diameters (1.6 mm and 1.0 mm), the method and site of embryo deposition (oviduct or uterus), the embryo development stage (2 - 4 cell or blastocyst), the method for oviduct or uterus stabilization, the potential for cryopreserved embryo transfer, the developmental potential of the embryos after transfer to the oviduct, patomorphology of the oviduct after transfer and possible clinical complications were taken into consideration. Two studies compared two variants of transfer to the uterus, and five variants of transfer to the fallopian tube. The transfer of embryos by the infundibulum may be of limited use due to handling problems and very low efficiency (pregnancy was not achieved). Very low efficiency was shown after transfer of vitrified embryos. Transfer to the fallopian tube by puncture of the fallopian tube, regardless of the developmental stage of the embryo, is the recommended method of embryo transfer. The histopathological examination of the fallopian tube revealed possible changes within the puncture site. The numerous clinical complications observed did not affect the effectiveness of the method.

Effectiveness of mind-body intervention on oocyte quality and serum cortisol level in sub-fertile women undergoing IVF treatment in Wardha region: A Study Protocol

In last 4 decades, the treatment of infertility has changed fundamentally and has been used increasingly in the whole world. Fresh embryo transfer and vitrified thawed embryo transfer are the two methods that are preferred. Nowadays, freeze all cycles are much more involved in the treatment of infertility. Maternal complications are found to be lesser in pregnancy arising from the cryopreserved thawed embryo transfers. Women undergoing frozen embryo transfer are found to have good ovarian reserve with a lower risk of preterm birth. But the occurrence of pregnancy-induced hypertension syndrome is found to be more in cryopreserved embryo transfer than in fresh embryo transfer. The ovarian hyperstimulation syndrome is found to be same in both types of embryo transfers. Objective of the study is to correlate the β-HCG outcome of fresh and frozen embryo shifting, to correlate pregnancy complications in patients with fresh and frozen embryo shifting, to identify various reasons for pregnancy complications and to establish criteria for selection of embryo transfer type (Fresh/Frozen). This invasive methodology includes a recording of the treatment history and the indications. Counseling of all the participants for research will be done. The further protocol includes evaluation of outcomes of both the techniques by comparing its complications in pregnancy.

THAWING BLASTOCYSTS FOR REPEAT OR DE NOVO PRE-IMPLANTATION GENETIC TESTING FOR ANEUPLOIDY WITH RE-VITRIFICATION: RESULTS AND OUTCOMES

Many patients opt for pre-implantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy and next generation sequencing (NGS) after completion of fresh IVF cycles (fresh-bx). A thaw-biopsy and refreeze of embryos that were not previously biopsied (single-bx TBR) or with no result after initial fresh biopsy (double-bx TBR) may also be indicated. Our study seeks to determine clinical pregnancy rates after cryopreserved embryo transfer (CET) of fresh-bx vs. single-bx TBR vs. double-bx TBR embryos.

Clinical outcome of embryo cryopreservation in Japanese breast cancer patients: pregnancy rates after transfer of thawed embryos.

To examine pregnancy outcomes after cryopreserved embryo transfer (ET) in breast cancer patients and to investigate the effect of controlled ovarian hyperstimulation (COH) as well as that of aromatase inhibitor (AI) administration and of the random start (RS) ovarian stimulation method. This retrospective study covered 126 patients who underwent embryo cryopreservation between 2010 and 2019. Thirty-one patients underwent frozen embryo transfer (FET), and we examined resulting pregnancy rates (PRs) and live birth rates (LBRs) in those who did and did not undergo COH and in relation to the AI and RS methods. PR and LBR per patient were higher among patients who underwent COH than among those who did not. PR per ET did not differ from that documented for non-cancer infertility patients, after adjustment for age. The PR and LBR did not differ between use and non-use of AI (27.8% vs 35.2%). In addition, there was no significant difference in the PR or LBR between RS and conventional start ovarian stimulation (33.3% vs 30.8%). No prenatal fetal abnormalities were observed in 8 cases (including 5 AI cases and 2 RS cases). This study showed that the outcome of FET after FP was equivalent to that seen in non-cancer patients. Further, neither use of AI nor the RS method influenced LBR. COH including use of AI and the RS method are useful in FP for collecting and freezing many embryos within a short period and for increasing the per patient LBR after cancer treatment.

P-274 Cycles with a high proportion of smooth endoplasmatic reticulum aggregates oocytes have a higher risk of transfer cancellation, but similar clinical outcomes after embryo transfer

Abstract Study question Are the clinical outcomes of an ICSI cycle impacted by the proportion of oocytes with smooth endoplasmatic reticulum aggregates (SERa)? Summary answer In terms of fertilization, blastocyst formation and live birth there is no difference between SERa- and SERa+ cycles, regardless of the proportion of SERa+ oocytes. What is known already It is not certain yet whether the presence of oocytes with SERa may impact the clinical outcome of an ICSI cycle. The majority of studies compare the outcome of SERa positive (SERa+) versus SERa negative (SERa-) cycles. It is not clear whether the proportion of SERa+ oocytes may play a role on cycles overall outcome, and which patients are at risk of harvesting a higher proportion of SERa+ oocytes. Limited data suggests that the duration of stimulation, the total dose of gonadotropins, the serum hormone levels and the number of oocytes are positively correlated with the presence of SERa+ oocytes. Study design, size, duration Retrospective study (2016-2019), including data from 2468 ovum pick-ups, performed in a tertiary university-based referral center. Results from fresh plus cryopreserved embryo transfers are included. In total, 2097 SERa- and 371 SERa+ cycles are included in the analysis. Participants/materials, setting, methods Cases are categorized based on the rate of SERa+ oocytes compared to the total number of metaphase II oocytes: SERa- (N = 2097), low SERa + (&amp;lt;30%) (N = 262), and high SERa + (≥30%) (N = 109). Baseline patient characteristics, treatment cycle parameters and clinical outcome per cycle are compared between the groups. According to the local protocol, SERa+ oocytes are not used for ICSI. Main results and the role of chance Women with high SERa+ proportion are older (36.15y for the SERa+ group vs. 34.49y for the high SERa- group, p &amp;lt; 0.001), have lower anti mullerian hormone levels (AMH) (1.60ng/ml vs. 2.28ng/ml, p &amp;lt; 0.001), received a higher total dose of gonadotropins (3227.01IU vs. 2858IU, p = 0.003), have fewer oocytes retrieved (9.13 vs. 11.08, p &amp;lt; 0.001), have a lower number of good quality day 5 blastocysts (1.17 vs. 2.33, p &amp;lt; 0.001) and face more often transfer cancellation (23.7% vs. 47.7%, p &amp;lt; 0.001). Compared to women with SERa- cycles, women with &amp;lt;30% SERa oocytes are younger (33.76y, p = 0.04), have higher AMH levels (2.56ng/ml, p &amp;lt; 0.001), have more oocytes retrieved (15.11, p &amp;lt; 0.001), have a higher number of good quality day 5 blastocysts (3.17, p &amp;lt; 0.001) and less transfer cancellations (14.9%, p &amp;lt; 0.001). A multivariate regression model adjusted for age, progesterone level at ovulation trigger and the type of pituitary suppression shows that cycles with a high proportion of SERa+ still have a lower amount of day 5 blastocysts (p &amp;lt; 0.001), a higher chance of transfer cancellation (p &amp;lt; 0.001), but no difference in the amount of retrieved oocytes (p = 0.097), fertilization (p = 0.813), blastocyst formation rate (0.975), implantation (p = 0.105) and live birth rate (p = 0.615). Limitations, reasons for caution The SERa+ oocytes in this analysis were not used for ICSI, which could have affected the result between SERa+ and SERa- cycles. Wider implications of the findings A low proportion of SERa+ oocytes (&amp;lt;30%) is common in young and high responders, without hampering clinical outcome. Contrary, &amp;gt;30% SERa+ oocytes leads to a higher risk of transfer cancellation, when these oocytes are not used for ICSI. Therefore, the inclusion of SERa+ oocytes for ICSI should be further investigated. Trial registration number not applicable

Effect of GnRH-a pretreatment before frozen-thawed embryo transfer on pregnancy outcome of adenomyosis-associated infertile patients with 56 cm3 ≤ uterine volume ≤100 cm3.

BackgroundWhether gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment before transferring frozen-thawed embryos (FETs) could improve the clinical outcome of adenomyosis-associated infertile patients with 56 cm3 ≤ uterine volume ≤100 cm3 is unclear.MethodsAdenomyosis patients who underwent in vitro fertilization and frozen embryo transfers from January 2009 to December 2019 with 56 cm3 ≤ uterine volume ≤100 cm3 were included in this retrospective cohort study. The subjects were divided into two groups (GnRH-a treatment group vs. GnRH-a-free group). The effect of GnRH-a treatment before FET on pregnancy outcomes was explored by univariate and multivariate analysis. In the GnRH-a treatment group, uterine volume before and after GnRH-a pretreatment was also compared by t-tests.ResultsA total of 186 patients undergoing 263 cryopreserved embryo transfer cycles were included. There was no significant difference in terms of the clinical pregnancy rate between patients in the GnRH-a treatment group (24/45, 53.3%) and the GnRH-a-free group (86/218, 39.4%) (P=0.098). The miscarriage rate in the GnRH-a treatment group (3/24, 12.5%) was significantly lower than that in the GnRH-a-free group (32/86, 37.2%) (P=0.044). The live birth rate in the GnRH-a treatment group (21/45, 46.7%) was significantly higher than that in the GnRH-a-free group (54/218, 24.8%) (P=0.009). However, the uterine volume did not change significantly before (82.0±13.4 cm3) or after GnRH-a treatment (79.3±14.0 cm3), with a P=0.123.ConclusionsGnRH-a pretreatment before FET reduced the miscarriage rate and improved the live birth rate among infertile women with adenomyosis whose uterine volume was 56–100 cm3.

Time-lapse KIDScoreD5 for prediction of embryo pregnancy potential in fresh and vitrified-warmed single-embryo transfers

Research question: Can KIDScoreD5 predict which blastocysts have the highest potential for achieving pregnancy?Design: A retrospective cohort study of 670 single fresh or frozen (FET) embryo transfer cycles was conducted between May 2019 and June 2021 at the Ottawa Fertility Centre, Canada. Blastocysts obtained from stimulated eligible cycles and cultured in a time-lapse incubator were selected for transfer or cryopreservation based on Gardner morphological scoring. Implantation and viable pregnancy rates were analysed retrospectively using KIDScoreD5 and Gardner scores associated with the transferred embryos. The predictive power of the KIDScoreD5 and Gardner assessment was evaluated using the average area under the curve (AUC) of the receiver operating characteristic curve.Results: KIDScoreD5 was positively correlated with implantation (r = 0.96, P = 0.002) and viable pregnancy (r = 0.96, P = 0.0001) rates. In fresh embryo transfer cycles, the AUC for implantation rate was significantly higher for KIDScoreD5 compared with Gardner scoring (0.70 versus 0.63, P = 0.03). For FET, significantly higher AUC were calculated for KIDScoreD5 than for Gardner scoring, for both implantation (0.64 versus 0.54, P = 0.002) and viable pregnancy (0.63 versus 0.53, P = 0.002) rates. When the ranking of cryopreserved embryos was based on KIDScoreD5, 46.2% of the FET cycles had at least one unused sibling embryo with a better KIDScoreD5 than the one selected for FET based on Gardner assessment.Conclusions: KIDScoreD5 predicts implantation and viable pregnancy rates of blastocysts better than Gardner morphological assessment in single fresh or cryopreserved embryo transfer cycles.

Association of embryo transfer type with infertility in endometriosis: a systematic review and meta-analysis.

The study aims to evaluate whether frozen embryo transfer can restore optimal receptivity leading to better assisted reproductive technology outcomes in women with endometriosis. This systematic review and meta-analysis, conducted from January 10, 2021 to July 1, 2021, searched the Cochrane Library, PubMed, Embase, Web of Science, OVID, and Clinicaltrials.gov databases from inception to January 10, 2021. The search strategy combined search terms as follows: ("endometriosis" OR "deep endometriosis" OR "endometrioma") AND ("frozen-thawed embryo transfer" OR "frozen embryo transfer" OR "freeze-all strategy") AND ("pregnancy outcome" OR "live birth rate" OR "clinical pregnancy rate" OR "miscarriage rate"). No publication time or language limits were set during the searches. In addition, references of the related articles were searched by hand. Patients were included if they had a history of endometriosis and had received fresh or frozen embryo transfer. Only the first transfer cycle was included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to express outcomes, and data synthesis was conducted using RevMan, version 5.4 software. A total of six studies with moderate methodologic quality were retrieved in the meta-analysis. The studies included 3010 women with endometriosis who wanted to conceive; 1777 (59.0%) had frozen embryo transfer, and 1233 (41.0%) had fresh embryo transfer. There was a significantly higher frequency of live births in the frozen embryo group than in the fresh embryo group (OR, 1.53; 95% CI, 1.13-2.08; P = .007). Despite a similar clinical pregnancy rate in the two groups (OR, 1.26; 95% CI, 0.95-1.69; P = .11), the difference in miscarriage rate was significant (OR, 0.70; 95% CI, 0.50-0.97; P = .03). Evidence quality was considered moderate. Cryopreserved embryo transfer has resulted in preferable reproduction outcomes when compared with fresh embryo transfer in patients with endometriosis, but the evidence is not yet abundant. More strictly designed research is needed to evaluate whether frozen embryo transfer leads to better reproductive outcomes in women with endometriosis compared with those receiving fresh embryo transfer. PROSPERO CRD42021248313.

Can endocrine characteristics of early pregnancy following natural cycle cryopreserved embryo transfer predict live birth?

Research questionCan serial measurements of serum oestradiol, progesterone and β-human chorionic gonadotrophin (HCG) concentrations, starting from the day of the first positive pregnancy test, predict live birth after natural cycle frozen-thawed embryo transfer (NC-FET)? DesignThis was a historical cohort study of women with a positive pregnancy test following NC-FET, between March 2009 and January 2020. Serum β-HCG, oestradiol and progesterone concentrations were measured on the day of the first pregnancy test and 48 and 96 h later. Pregnancies resulting in a live birth were compared with non-viable pregnancies. ResultsOf 101 women with a positive pregnancy test included in the study, 78 had a live birth and 23 had a non-viable pregnancy. Serum β-HCG concentrations were comparable on the day of the first pregnancy test (P = 0.09) but became significantly higher in women with a live birth 48 and 96 h later (P = 0.018 and P = 0.003). Serum oestradiol concentrations were higher in women with a live birth at all three measurements (P = 0.02, P = 0.007 and P = 0.02). Serum progesterone concentrations were higher 48 h after the first pregnancy test in women with a live birth (P = 0.04). On multivariate analysis, after controlling for the women's ages and number of embryos transferred, serum concentrations above the 25th percentile for oestradiol (>488–526 pmol/L) and progesterone (>63–70 nmol/L) were independent predictors of live birth at all three measurements. ConclusionsIncreased serum oestradiol and progesterone concentrations in early NC-FET pregnancies are associated with increased likelihood of live birth. Oestradiol and progesterone concentrations can be used in conjunction with β-HCG to predict pregnancy viability and assist in patient counselling.