FET Cycles Research Articles

P–682 Serum progesterone level as prognostic factor in frozen-thawed embryo transfer cycles: effect of selected threshold on gestational results. Systematic review, stratified meta-analysis and meta-regression

Abstract Study question Is there an optimum progesterone threshold level below which gestational results are significantly worse in frozen embryo transfer cycles (FET) with hormone replacement therapy (HRT)? Summary answer Low serum progesterone during luteal phase of HRT-FET cycles impairs substantially its gestational outcomes, regardless of threshold level, origin of oocytes and euploidy of embryos. What is known already HRT for endometrial preparation in FET or oocyte donation cycles is widely used. Oestrogen doses are usually patient-tailored varying upon endometrial thickness, whereas the optimal level of progesterone exposure has not been defined. Various studies have found a negative association between serum progesterone levels measured during luteal phase and FET results in terms of pregnancy and miscarriage rates. Most likely there is an optimal level below which results are worse but a standard threshold level is yet to be established, as in almost every study a different threshold has been found. Study design, size, duration Systematic review and stratified meta-analysis with meta-regression following PRISMA guidelines. An electronic search of MEDLINE, EMBASE, Web of Science, Cochrane Gynaecology and Fertility Specialised Register of Controlled Trials and ClinicalTrials.gov was conducted from inception to January 2021. The aim was to identify prospective or retrospective cohort studies measuring serum progesterone levels around frozen embryo transfer date in HRT cycles. A combination of the following key search terms was used: “progesterone”, “serum”, “frozen embryo”, “transfer”, “frozen-thawed”. Participants/materials, setting, methods Studies analyzing association of luteal serum progesterone with FET-HRT outcomes were included. Risk of bias within studies was assessed using the Newcastle-Ottawa Scale (NOS). Clinical/ongoing pregnancy and miscarriage rates (C/OPR,MR) were considered as primary and secondary outcomes respectively. Odds Ratios with 95% Confidence Interval (OR,95%CI) were calculated applying a random effects model meta-analysis. Heterogeneity was assessed using the I2 statistic. A meta-regression was conducted to examine the association of the effect with the threshold level. Main results and the role of chance The systematic search retrieved 792 studies, 494 after duplicates removal of which 343 were screened and 51 assessed for eligibility. 12 studies, reporting 14 threshold levels, were included in the meta-analysis involving 5009 HRT-FET cycles. Two of them were prospective cohort studies while the rest were retrospective. 10 of them have been published in peer review journals and two were conference abstracts. Quality of studies assessed with NOS varied between 5 and 9. The progesterone threshold ranged from 5.0 to 21.94 ng/ml. Low progesterone levels were associated with less C/OPR (OR: 0.52; 95% CI: 0.40 to 0.66; 11 studies, 5009 cycles). Low progesterone was also associated with high MR (OR: 2.01; 95% CI: 1.57 to 2.58; 9 studies, 2560 pregnancies). These effects showed remarkable consistency in specific sub-analyses considering separately studies with progesterone thresholds up to or above 10 mg/mL, and studies carried out in cycles using oocyte donation, autologous oocytes and embryo aneuploidies screening. Meta-regression did not identify significant association between size effect and progesterone threshold, regarding neither C/OPR (regression coefficient: 0.02; CI 95%: –0.02 to 0.06; p: 0.28) nor MR (regression coefficient: 0.11; CI 95%: –0.13 to 0.36; p: 0.32). Limitations, reasons for caution High degree of clinical and statistical heterogeneity was found due to different routes and doses of progesterone administration, date of progesterone analyses and variety of thresholds as well as high diversity of embryo origin. Despite sensibility analysis by embryo origin any of these sources of heterogeneity can preclude the results. Wider implications of the findings: Despite low progesterone levels are significantly associated to lower gestational results, and a threshold of 10 ng/ml constitutes the median value of our distribution, high quality prospective studies are needed to validate the prognostic value of progesterone levels and to establish an standardised threshold level for clinical application. Trial registration number not required

P–237 The good, the fast and the slow: which is better? Live birth rate following single blastocyst frozen embryo transfer

Abstract Study question Are embryo quality and day of vitrification (Day 5, 6 or 7) associated with live birth rates (LBR) following single blastocyst transfer (SBT) in frozen embryo transfer cycle (FET)? Summary answer Both blastocyst quality and day of vitrification are significantly associated with LBRs, with very low LBR when poor quality embryos are frozen on day 6. What is known already Evidence suggests that chromosomal status (ploidy) is strongly associated with blastocyst morphology and good quality embryos are more likely to be euploid. Furthermore, previous studies have shown a relationship between the time that embryos need to reach blastocyst stage and their euploidy rate with slowly developing blastocysts showing higher rate of aneuploidy. Nonetheless, despite all this evidence little is known about the actual effect of the combination of blastocyst quality and day of its vitrification. The scope of this study was to quantify the actual effect of the embryo quality and day of vitrification on live birth rates following FET. Study design, size, duration Retrospective analysis of 1546 FET cycles with SBT conducted between 2017 and 2019 in the university-affiliated private clinic. The embryos used for FET were obtained from IVF/ICSI: with PGT (FET-PGT) or without PGT (FET0) or from donated oocytes (FET-DON). Participants/materials, setting, methods FET with natural, natural-modified and completely medicated cycles to prepare endometrial lining were included. Blastocysts were classified according to Spanish Association for the Study of Reproductive Biology (ASEBIR) classification, ranging from A (the highest) to D (the lowest). The impact on LBR of different subgroups, formed within FET-PGT, FET0, FET-DON groups due to different day of vitrification and blastocyst quality, was assessed, using logistic regression after adjusting for age, day of vitrification and embryo quality. Main results and the role of chance We included 1546 FET cycles. Of those, 543 (35%) corresponded to FET-PGT; 648 (42%) to FET0 and 355 (23%) to FET-DON cycles. Overall, 1051 (68%) embryos were frozen on day 5(D5), 472 (30.5%) on day 6(D6) and 23 (1.5%) on day 7(D7). As far as embryo quality was concerned, 215 (13.9%) grade A; 957 (61.9%) B; 371(24%) C and 3(0.2%) D blastocysts were transferred. LBRs were significantly different between different embryos frozen on D5 44.3%; on D6 28.8% and on D7 8.7%, p < 0.001. When blastocyst quality was considered, LBR were 48.4% for grade A; 42.5% for B; 25.1% for C and 0% for D, p < 0.001. After applying logistic regression analysis, the odds ratio (OR) for transferring D6-blastocyst was 1.08, 95% CI[0.45; 2.62] and blastocyst with grade B and C; 0.71, 95% CI[0.51; 1.00]; 0.57,95% CI[0.36; 0.88] respectively. However, after transferring D6-blastocyst graded as C, the OR was 0.33, 95% CI[0.12; 0.90]. Our predictive model showed that the impact of the embryo quality on LBR was sustained across three groups. Transfer of D5/D6 grade A blastocyst resulted in the highest, while D6-C in the lowest LBR in all the groups. In the latter case vitrification on D6 impaired additionally the outcome. Limitations, reasons for caution The study should be interpreted with caution due to its retrospective character and the assessment of blastocyst quality on the day of vitrification and not on the day its transfer. Wider implications of the findings: Our robust findings could be considered a useful tool for counselling couples who seek advice regarding their expected success rates in the setting of FET with SBT. The very low livebirth rates in low quality (C) slow developing (D6) embryos should be communicated to patients prior to planning a FET. Trial registration number Not applicable

P–649 Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis

Abstract Study question Should women receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET)? Summary answer Progesterone LPS following NC-FET increases the live birth rate. There is no evidence to support the administration of hCG for LPS in these cases. What is known already Whether or not women should receive LPS following NC-FET is highly controversial. Previous studies have shown conflicting results. Study design, size, duration We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of study-design. The search strategy included keywords related to natural cycle frozen embryo transfer and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. Participants/materials, setting, methods Our systematic search generated 395 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG, and 6 studies (n = 1507) used progesterone for luteal support. Four studies were randomized controlled trials (RCTs), whereas the other four were historic cohort studies. Main results and the role of chance In a meta-analysis using random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (two studies, OR 0.85, 95% CI 0.64–1.14). On the other hand, progesterone LPS was associated with a higher clinical pregnancy rate (five studies, OR 1.48, 95% CI 1.14–1.94), and a higher live birth rate (three studies, OR 1.67, 95% CI 1.19–2.36). Limitations, reasons for caution There was large heterogeneity in progesterone dose and route of administration, as well as the methods used for ovulation detection and triggering. Moreover, only four studies were randomized. Finally, both studies examining the use of hCG for LPS were performed by the same group of researchers in a single center. Wider implications of the findings: The available evidence indicates that progesterone administration for LPS is beneficial following natural cycle frozen embryo transfer. There is no evidence to support the administration of hCG for LPS in these cases. Additional Large RCTs are necessary in order to improve the quality of evidence and validate our findings. Trial registration number PROSPERO ID: CRD42020199045

OUTCOMES OF FROZEN DONOR OOCYTES COMPARED TO FRESH DONOR OOCYTES CYCLES, AN INTENT TO TREAT ANALYSIS

Since the ASRM designated egg freezing as a standard method for fertility preservation and no longer experimental in 2012, the prospect of changing the paradigm of egg freezing has become a reality. However, due to the relative newness of this technology and variable success of egg freezing techniques many providers are hesitant to use this method of oocyte donation to their patients out of a concern for lower success rate compared to the traditional model of fresh direct oocyte donation. Compare outcomes of frozen donor egg thaws to the traditional fresh oocyte donation model. Retrospective cohort study in a single academic fertility center. All anonymous donor-egg recipients, undergoing IVF between 2016-2020 at a single academic center were included for analysis. An egg thaw or egg retrieval was considered a cycle for analysis. All frozen oocytes were fertilized with ICSI and insemination method for fresh donor egg cycles were determined by semen parameters and physician recommendation. PGTA was performed at the request of the recipient couple. If PGTA was performed, embryos were biopsied at the blastocysts stage and refrozen while waiting for genetic test results, then subsequently transferred in a FET cycle. Cycle outcomes such as fertilization, blast formation, total number of usable blastocysts, implantation rate per embryo transfer and total cycle potential were compared. Liver birth rate was calculated per cycle start and per transfer. Miscarriage rate was calculated per pregnancy. Fifty-seven and 42 insemination cycles using fresh direct donor oocytes and frozen donor oocytes from egg bank respectively were analyzed. The average number of MII oocytes were 14.5 and 6.0 in fresh and frozen donor oocytes groups, respectively. Fresh donor oocyte cycles resulted in higher chance to have more than one embryo available for transfer or biopsy (89.5% vs 57.1%, p < 0.001). Fresh oocyte cycles were more likely to utilize PGT-A for elective single embryo transfer (56.1% vs 11.9%, p < 0.001). In cycles using fresh donor oocytes, 47.3% (27/57) had more than one embryo transfers vs 11.4% (4/42) in frozen donor oocytes group. The live birth rates after the first embryo transfer (42.1% vs 38.1%, p = 0.688) were similar in two groups however the cumulative live birth rates per cycle to start was higher in fresh oocyte donor group (75.4% vs 42.9%, p < 0.001). A significantly lower miscarriage rate was noted with embryos derived from fresh donor oocytes (2.4% vs 18.2%, p = 0.028). Live birth rate per cycle to start is higher using fresh donor oocytes versus cryopreserved oocytes from egg bank, likely due to more surplus embryos after completion of the first embryo transfer. An increased risk for miscarriage rates was observed in frozen donor oocytes group. Large sample size studies are needed to investigate whether frozen oocyte donor from egg bank is a more cost-effectiveness strategy compared with fresh oocyte donor.

Does Adenomyosis Influence ICSI Clinical Outcome? A Systematic Analysis and Impact of GnRH Agonist Pretreatment for Women with Adenomyosis in ICSI-FET Cycle: A Retrospective Cohort Study.

To evaluate the impact of adenomyosis on pregnancy outcome in ICSI/FET cycles and the beneficial effect of GnRH agonist pretreatment, conservative surgery or combination therapy on pregnancy outcome. This is a retrospective cohort study where 613 ICSI cycles done in the period from Jan 2018 to Dec 2020 in Sudha infertility centre, Erode were analyzed. Study populations include 235 women with adenomyosis undergoing ICSI/FET cycle. Overall, the outcome in terms of clinical pregnancy rate, miscarriage rate, live birth date and ongoing pregnancy rate was lower in women with adenomyosis following ICSI/FET cycles. We found significant improvement in clinical pregnancy rate who had pretreatment with GnRH agonist, conservative surgery or combination therapy. Adenomyosis as such has detrimental effect on ICSI clinical outcome. Pretreatment with GnRH agonist and conservative surgery and GnRH agonist long protocol could be beneficial. Further large scale prospective comparative studies are needed to confirm this result.

The Association Between Serum Estradiol and Progesterone On the Same Day of FET and The Pregnancy Outcome; A Cross Sectional Study

Research Question Precise timed synchronization between endometrium and the embryo is essential for high implantation and pregnancy rate, it is worthy to mention that endometrial thickness is not the only factor, E2 and P levels are also regularly monitored for endometrial receptivity. So, we decided to go for this study, to investigate the impact of serum E2 and P levels on the same day of embryo transfer on pregnancy outcomes for FET cycles. Design This was a retrospective cross sectional study for 402 FET cycles which conducted between April 2018 and May 2019. All participants started endometrial preparation for FET with 6 mg/day oral estradiol for 13 days. When endometrium reached 8 mm or greater, patients were initiated on both micronized vaginal and oral P treatment. On FET day, serum level of E2 and P were assessed. Then, transfer of PGT euploid embryos was performed. 12 days’ later pregnancy test was assessed, and then 4 weeks after FET date ultrasound was scheduled to check the viability and the clinical pregnancy. Results The mean E2 value was 931.41 ± 438.65 pg/ml, while mean P value was 8.47 ± 9.4 ng/ml. 240 out of 402 cases got pregnant (59.7%) while the clinical pregnancy rate was 53.9% with no correlation between serum (E2, P &amp; E/P ratio) and the outcome. Conclusion Our results revealed that the association between E2 and P on FET day and the pregnancy outcome is still not proven and those markers can’t serve as predictors for the outcome.

Thin endometrial lining during frozen embryo cycles: a case-control study of risk factors and natural history

Objective: To identify predictors of thin endometrial lining in the first frozen embryo transfer cycles and to characterize the natural history of this condition over subsequent cycles. Design: Retrospective case-control study Conclusions: This study shows that prognosis after a diagnosis of thin endometrial lining is favorable. Lower weight and thinner fresh cycle lining are predictors of thin endometrial lining in FET cycles. Most importantly, women with a diagnosis of thin endometrial lining have similar live birth rates as those with adequate endometrial lining, although their time to achieve live birth is slightly longer.

Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study.

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)? PGT-A use was associated with improved live birth rates in couples with recurrent pregnancy loss undergoing frozen embryo transfer (IVF-FET). Euploid embryo transfer is thought to optimize outcomes in some couples with infertility. There is insufficient evidence, however, supporting this approach to management of recurrent pregnancy loss. This study included data collected by the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART-CORS) for IVF-FET cycles between years 2010 through 2016. A total of 12631 FET cycles in 10060 couples were included in this analysis designed to assess the utility of PGT-A in couples with RPL undergoing FET, including 4287 cycles in couples with tubal disease who formed a control group. The experimental group included couples with RPL (strictly defined as a history of 3 or more pregnancy losses) undergoing FET with or without PGT-A. The primary outcome was live birth rate. Secondary outcomes included rates of clinical pregnancy, spontaneous abortion, and biochemical pregnancy loss. Differences were analyzed using generalized estimating equations logistic regression models to account for multiple cycles per patient. Covariates included in the model were age, gravidity, geographic region, race/ethnicity, smoking history, and indication for assisted reproductive technologies. Analyses were stratified for age groups as defined by SART: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. In women with a diagnosis of RPL, the adjusted odds ratio (OR) comparing IVF-FET with PGT-A versus without PGT-A for live birth outcome was 1.31 (95% CI: 1.12, 1.52) for age <35 years, 1.45 (95% CI: 1.21, 1.75) for ages 35-37 years, 1.89 (95% CI: 1.56, 2.29) for ages 38-40, 2.62 (95% CI: 1.94-3.53) for ages 41-42, and 3.80 (95% CI: 2.52, 5.72) for ages >42 years. For clinical pregnancy, the OR was 1.26 (95% CI: 1.08, 1.48) for age <35 years, 1.37 (95% CI: 1.14, 1.64) for ages 35-37 years, 1.68 (95% CI: 1.40, 2.03) for ages 38-40 years, 2.19 (95% CI: 1.65, 2.90) for ages 41-42, and 2.31 (95% CI: 1.60, 3.32) for ages >42 years. Finally, for spontaneous abortion, the OR was 0.95 (95% CI: 0.74, 1.21) for age <35 years, 0.85 (95% CI: 0.65, 1.11) for ages 35-37 years, 0.81 (95% CI: 0.60, 1.08) for ages 38-40, 0.86 (95% CI: 0.58, 1.27) for ages 41-42, and 0.58 (95% CI: 0.32, 1.07) for ages >42 years. The retrospective collection of data including only women with recurrent pregnancy loss undergoing FET presents a limitation of this study, and results may not be generalizable to all couples with recurrent pregnancy loss. Also, data regarding evaluation and treatment for RPL for the included women is unavailable. This is the largest study to date assessing the utility of PGT-A in women with RPL. PGT-A was associated with improvement in live birth and clinical pregnancy in women with RPL, with the largest difference noted in the group of women with age greater than 42 years. Couples with RPL warrant counseling on all management options to reduce subsequent miscarriage, which may include IVF with PGT-A for euploid embryo selection. There are no conflicts of interest to declare. N/A.

Effect of embryo cryopreservation duration on pregnancy-related complications and birthweight after frozen-thawed embryo transfer: a retrospective cohort study.

Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4-6 months, 7-12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.

Comparison of vaginal progesterone gel combined with oral dydrogesterone versus intramuscular progesterone for luteal support in hormone replacement therapy-frozen embryo transfer cycle

BackgroundIt remains under subject of debate regarding the optimal route of luteal support for hormone replacement therapy- frozen embryo transfer (HRT-FET) cycles. We compared efficacy of vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone for HRT-FET lutein support. MethodsThis is a retrospective observational study. After matching for propensity score of getting vaginal + oral treatment, a total of 208 FET cycles in the vaginal progesterone combined with oral dydrogesterone and 624 cycles in the intramuscular progesterone group were enrolled. Pregnancy outcomes and neonatal outcomes including chemical pregnancy rate, clinical pregnancy rate, implantation rate, spontaneous abortion rate, live birth rate, gestational weeks, pre-term delivery, birth weight, and congenital anomalies rate were compared. ResultsNo significant differences were observed in patient characteristics such as age, duration of infertility, type of infertility, or hormone level after matching. Chemical pregnancy rate (68.3 % versus 70.5 %), clinical pregnancy rate (64.9 % versus 64.4 %), implantation rate (52.3 % versus 50.2 %), spontaneous abortion rate (21.5 % versus 18.4 %), and live birth rate (49.0 % versus 51.3 %) were similar in both group without statistically significant difference. No significant differences in neonatal outcomes were observed between the two groups. ConclusionWe observed similar pregnancy outcomes in both vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone protocol. Vaginal progesterone gel combined with oral dydrogesterone can be substituted for intramuscular progesterone given that vaginal plus oral use has good safety and is more convenient and may be associated with less side effect caused by intramuscular injection.

“Does serum estrogen level have an impact on outcomes in hormonal replacement frozen-warmed embryo transfer cycles?”

Aim To evaluate the impact of serum estradiol (E2) levels on cycle outcomes in hormone replacement frozen embryo transfer (HR- FET) cycles. Materials and methods We retrospectively analyzed 509 HR-FET cycles performed from September 2018 to September 2019. Patients were divided into 6 groups based on their E2 values measured a day before progesterone initiation . Group 1: <100 pg/mL, group 2: 100–200 pg/mL, group 3: 200 − 300 pg/mL, group 4: 300–400 pg/mL, group 5: 400–500 pg/mL, group 6: >500 pg/mL. Implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), multiple pregnancy rate (MPR) and ectopic pregnancy rates were compared between all groups. Results IR and CPR were similar between a wide range of E2 values, but when E2 values were more than 500 pg/mL there was a non significant fall in the IR (47.3% vs 48.3% vs 48.6% vs 47.8% vs 48.7% vs 39.6% p = .77) and CPR (63.6% vs 65.1% vs 65.6% vs 65.3% vs 65.6% vs 53.1% p = .692). MR was significantly high when E2 was less than 100 pg/mL (28.5%) and when E2 was more than 500 pg/mL (41.1%) (p = .02). MPR and ectopic pregnancy rates were similar between all the groups Conclusion Outcomes of FET cycles were similar between a wide range of E2 values (100–500 pg/mL). When E2 levels were less than 100 pg/mL or more than 500 pg/mL there was significant increase in the MR but the numbers in these groups are less and further studies are required to confirm these facts.

Endometrial Receptivity In Art Cycles: A Review On Different Aspects Of Improvement

Background: 65% of the causes of infertility are related to female factors. Receptive endometrium is essential for a successful pregnancy. In ART cycles, receptivity is not achieved optimally. Main body: Uterine receptivity is the ability of the uterus to accept a competent blastocyst. The factors affecting endometrial receptivity include: hormonal, genetic and immunological factors. During the receptive phase, different changes occur in endometrium (Cytoskeletal, biochemical and genetic). This review article discusses the interventions that can improve the uterine receptivity in ART cycles. Conclusion: PRP has growth factor and anti-inflammatory properties. It is safe and it has positive effects on endometrial receptivity. Endometrial scratching may be associated with the secretion of growth factors and cytokines involved in the wound healing process and may also contribute to enhancing the embryo implantation. Acupuncture is effective as a complimentary medicine and should be used along with routine medical approaches. Medications like aspirin, growth hormone and heparin that are used in ART cycles improve the receptivity. Use of stem cells in human is limited and although they have positive effects on animals, they have a long way to be safe enough to be used for human. Nutritional supplements like Carnitines, vitamin E and melatonin seems to be safe and effective in endometrial receptivity. In FET cycles, developmental synchrony between the embryo and uterus is maintained. Endometrial receptivity assay (ERA) was introduced as an accurate molecular tool to determine the endometrial receptivity status.

Reproductive Outcomes of Single Embryo Transfer in Women with Previous Cesarean Section.

The aim of this study is to evaluate the reproductive outcomes of patients with previous cesarean section (CS) undergoing single-embryo transfer (SET). A total of 5479 patients previously underwent CS or vaginal delivery (VD) were included. The patients with previous CS included single/double cleavage (SCT/DCT), single/double blastocyst stage embryo transfer (SBT/DBT). The comparison of reproductive outcomes between CS and VD, SET, and double-embryo transfer of CS was conducted. The main outcome measures included clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), live birth rate (LBR), and cumulative live birth rate (CLBR). There were no differences in CPR and LBR between patients previously underwent CS and VD, and the preterm birth rate of multiple births in patients underwent CS were significantly higher than underwent VD. As for patients underwent CS, the CPR, MPR, and LBR were lower in patients treated with SCT than DCT in IVF/ICSI cycles. The CPR and LBR of patients treated with SCT were not statistically different compared with DCT and SBT when patients' age were younger than 35years in FET cycles, and the MPR of patients treated with SCT was lower. The CPR and LBR of patients treated with SCT were lower than DCT/SBT when patients' age were 35years or older in FET cycles. The CPR, LBR, and CLBR of patients treated with SBT were not lower than DCT in IVF/ICSI-ET, FET, and complete cycles, but the MPR was lower. Reducing the number of embryos transferred should be considered seriously for CS. SCT under the 35years of FET cycles is feasible. SBT is an effective strategy to reduce MPR of IVF/ICSI, FET, and complete cycles regardless of overall or age stratification.

Predicting and improving the probability of live birth for women undergoing frozen-thawed embryo transfer: a data-driven estimation and simulation model

Background and objectiveFrozen-thawed embryo transfer (FET) is now widely used for the treatment of infertility. For many couples and clinicians, concerns over the probability and how to increase the chance of a successful birth are very common. Currently, there is not a single model to predict the live birth outcomes for FET. To estimate the probability of live birth (PLB) in FET and to provide advice on potential treatment options by a data-driven predictive (DDP) model. Methods2,189 FET cycles from Jan 2012 to Dec 2015 were recruited in a single center. 815 cycles of FET outcomes were live births and 1,374 cycles of FET outcomes failed. To verify the consistency of the DDP model, we carried out 10-fold cross-validation, and the mean and standard deviation of the accuracy were measured. Moreover, the performance of this model was evaluated by the mean and standard deviation of receiver operating characteristic curve and area under the curve (AUC). ResultsNine dominant factors, including age, BMI, HOMA-IR, basal follicle stimulating hormone, basal luteinizing hormone, basal estradiol, endometrial thickness, the number of embryo transfers and the total number of embryos, were automatically extracted from 28 candidate factors. The accuracy of our prediction model is 76.9%±1.6%, and the AUC is 0.83. Then, the PLB is estimated by the random forest algorithm. On this basis, the DDP model can comprehensively traverse and dynamically visualize the impact of several factors on live birth outcomes. Finally, optimal suggestions for the treatment of patients before FET are attempted to be made by the genetic algorithm. ConclusionThe DDP model can not only provide satisfactory performance for predicting live birth outcomes in FET but also offer a visual estimation and simulation tool for clinicians to make treatment plans.

IMPACT OF ENDOMETRIAL PATTERN ON LIVE BIRTH RATE AND SUBSEQUENT DEVELOPMENT OF HYPERTENSIVE DISORDERS OF PREGNANCY

Recent studies suggest that FET cycles are associated with a higher incidence of hypertensive disorders of pregnancy (HTN). In FET cycles, endometrial thickness and pattern have been used as indicators of endometrial receptivity, although the ability of these measures to predict clinical pregnancy rate (CPR), live birth rate (LBR), and pregnancy complications remains unclear. The current study examines the influence of endometrial pattern (EP) and thickness on CPR, LBR, and HTN.

ASSOCIATION BETWEEN ESTRADIOL LEVELS AND OBSTETRIC OUTCOMES IN LETROZOLE-STIMULATED FROZEN EMBRYO TRANSFER CYCLES

Letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles are increasingly utilized due to growing evidence of improved success rates in multiple populations, including patients with polycystic ovary syndrome, diminished ovarian reserve, tubal factor, or unexplained infertility. The degree of estrogen suppression is variable between patients, and the impact of low estradiol (E2) levels in the follicular phase is unknown. Thus, the goal of this study was to assess the impact of low estradiol on outcomes of LTZ- FET cycles.

CLOMIPHENE CITRATE EXPOSURE DOES NOT ADVERSELY AFFECT CLINICAL OUTCOMES IN SINGLE, EUPLOID FET CYCLES

Clomiphene citrate (CC) is a selective estrogen receptor modulator utilized for OI and COH. Pharmacologically, CC has a half-life of 5 days; yet, it can be excreted after 6 weeks after initial administration1. CC is known to have antioestrogenic side effects which had been associated to a reduction in implantation rates for patients who undergo fresh IVF cycles2. However, evidence is scarce about the effect of CC on implantation potential in FET cycles. One study showed that patients who undergo a FET within 90 days after CC treatment had lower pregnancy rates compared with FET cycles that occur after 90 days of CC treatment 3.

OPTIMIZING FROZEN EMBRYO TRANSFER (FET) SUCCESS: IMPROVED SUCCESS IN NATURAL CYCLES WITH THE USE OF HCG TRIGGER DESPITE SIMILAR OVERALL OUTCOMES WITH GONADOTROPIN STIMULATED, NATURAL, AND PROGRAMMED CYCLES

To evaluate reproductive outcomes in FET cycles following hormonally programmed cycles vs alternate regimens of gonadotropin stimulated cycles or natural or letrozole-induced cycles. Within natural and letrozole cycles, pregnancy rates with and without hCG trigger to induce ovulation were compared. Retrospective cohort study. All programmed, natural cycle, letrozole, and gonadotropin stimulated FETs from a single academic center from 2017 – 2020 were evaluated. Programmed cycles consisted of oral micronized estradiol 2 mg TID starting day 1 of menses followed by intramuscular progesterone. Gonadotropin stimulated cycles consisted of ovulation induction with FSH and/or hMG starting on Day 1-5 of menses followed by hCG injection (“trigger”), with vaginal or intramuscular progesterone in the luteal phase. Natural cycles involved no medication in the follicular phase, whereas letrozole cycles consisted of letrozole 5 mg cycle day 3-7. For both natural and letrozole cycles, transfer was timed either to the patient’s own ovulation as measured by serum LH and progesterone or by ovulation induced by hCG trigger. Vaginal progesterone was used for luteal support. For the primary analysis, natural and letrozole cycles were included together in the natural group. One way- ANOVA was performed to compare baseline variables between cohorts. Chi-square was used to compare pregnancy outcome variables. Fisher’s Exact test was used to compare two groups when appropriate due to sample size. A p value <0.05 was considered significant. A total of 784 FETs were included: 728 programmed FETs, 24 natural cycle FETs, and 32 gonadotropin stimulated FETs. No statistical difference was found between all 3 cohorts based on age, BMI, endometrial thickness, or number of embryos transferred. Clinical pregnancy rates (CPR) or implantation rates (IPR) did not differ between programmed, natural/letrozole cycles, or gonadotropin stimulated FETs (54.3% vs 41.7% vs 59.4%, p=0.4) (46.3% vs 42.3% vs 48.8%, p= 0.9) respectively. Live birth/ongoing pregnancy rates were also not different (43.3% vs 41.7% vs 56.3%, p=0.3). Additionally, miscarriage rates did not differ between groups (10.3% vs 0% vs 3.1% p = 0.1). A subset analysis of natural cycle FETs showed no difference in letrozole induction versus spontaneous ovulation CPR (40% vs 42.9%, p=0.99), however natural/letrozole cycles with hCG trigger were associated with an increase in CPR (75% vs 25%, p=0.032). Our center utilizes stimulated FET cycles as an alternative for patients who do not achieve appropriate endometrial growth with traditional programmed FET. Our findings suggest stimulated FET cycles can be a successful alternative for patients whose lining is not appropriate in a programmed FET cycle. We use letrozole or natural cycle FETs in patients for whom a programmed or stimulated FET is not appropriate, with similar success rates. However, our study suggests use of an hCG trigger may improve outcomes in natural or letrozole cycles.

IS EARLY HCG PREDICTIVE OF PREGNANCY AFTER ESET IN BOTH FRESH AND FET CYCLES?

Most ART programs perform β-hCG measurement 9-12 days after embryo transfer(ET) to detect a pregnancy. A prior study using hyperglycosylated hCG in a small sample size showed that a single measurement 6 days after ET had 100% sensitivity and specificity in identifying biochemical and ongoing pregnancies. We sought to determine whether routine serum β-hCG measurement at 5-6 days after ET is predictive of ART outcome. This is important in patient counseling if we can stop P supplementation early in cases of negative tests, especially if taking painful IM P supplementation. Prospective single center. A total of 241 patients undergoing eSET (elective single embryo transfer) had their “early” serum β-hCG measured 5-6 days after ET, and the “official” serum β-hCG was done 9-10 days after ET. There were 91 fresh ET and 150 FET cycles. A test was positive if the β-hCG measurement was ≥ 3 IU/L. All tests were performed at a commercial laboratory with offices around the US (LabCorp). In the 91 fresh ET cases observed, 65 had positive and 26 had negative “early”β-hCG tests measured 5-6 days post ET. Of the 65 positive β-hCG tests, 10 (15.4%) were biochemical, 9 (13.8%) were pregnancy losses (SAB), and 46 (70.8%) were live births. Of the 26 negative tests, 24 (92.3%) were negative on days 9-10 and 2 (7.6%) were positive on days 9-10. Both positive results on day 9-10 ended with biochemical losses. In the 150 FETs observed, 81 had positive and 69 had negative “early” β-hCG. Of the 81 positive, 19 (23.5%) were biochemical pregnancies, 7 (8.6%) had SAB, and 55 (67.9%) were ongoing/live births. Of the 69 negative β-hCG tests measured 5-6 days post FET, 4 (5.7%) were then positive on day 9-10, 3 resulting in biochemical pregnancies and one live birth. The mean “early” β-hCG levels in the IVF group was 27.03 IU/L which was significantly higher than in the FET 14.09 IU/L (P<0.001). There were significant differences in early β-hCG results between ongoing/delivered and biochemical pregnancies in both fresh and FET groups (P<0.001), but not between ongoing/LB and SAB. However, by first β-hCG level on days 9-10 there were no differences in the mean β-hCG between the 2 groups (P=0.04). ROC for fresh ET showed a cut off value of 7 IU/L. The test can detect with 90% sensitivity a 96% specificity with 3.8% false positive (AUC=0.972). For FET it showed a cut off value of 3.7 IU/L. The test can detect with 89% sensitivity a specificity of 94% with 5.7% false positive (AUC=0.964) (Figure 1). Early serum β-hCG measured 5-6 days after ET in eSET cycles is very predictive of successful pregnancies. A negative test 5-6 days after ET is associated with a negative 9-10 day β-hCG test in both fresh and FET cycles. In the fresh group, an early negative β-hCG was 100% predictive of no live births, but in the FET group an early negative in the FET group led to a single live birth (99.33% predictive of no live births). FET cycles were associated with lower early β-hCG levels than fresh transfers but became similar to fresh cycles on the first day of actual pregnancy test. This information is of potential benefit in counseling women undergoing ART.

EFFECT OF BODY MASS INDEX (BMI) ON PREGNANCY OUTCOMES IN FROZEN-THAWED BLASTOCYST TRANSFER (FET) CYCLES

There is limited and conflicting data from either small or non-US cohorts on the effect of body mass index on pregnancy outcomes in FET cycles. We aimed to investigate the effect of BMI on ongoing pregnancy rate (OPR) in FET cycles in a larger US cohort.