Fresh Cycles Research Articles

#390 : Why Our Clinical Pregnancy Rates Have Improved Over the Past Two Years: Exploring Key Points of Gonadotropin-Releasing Hormone Antagonist Protocol in Fresh Embryo Transfer Cycles

Background and Aims: GnRH-ant protocol is effective in preventing a surge of pituitary luteinising hormone during controlled ovarian stimulation. In recent years, GnRH-ant protocol has been optimised to improve in vitro fertilisation outcomes. However, firstly, the success rate of frozen embryo transfer is consistently better than that of fresh embryo transfer and secondly, the success rate of GnRH-ant protocol on fresh embryo transfer is lower than that of the long protocol. This study aims to draw out a comparison of before and after data from our own centre to find the reasons for the gradual maturation of GnRH-ant protocol on fresh embryo transfer. Our study proposed to investigate the determinants affecting fresh embryo transfer in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Method: We reviewed 2464 fresh embryo transfer cycles for IVF/ICSI-ET assisted reproduction techniques performed at our centre from 1 January 2015 to 31 December 2019. The exclusion criteria were as follows: endometriosis grade III to IV (American Fertility Society classification of endometriosis); adenomyosis; severe male oligospermia or obstructive azoospermia. Firstly, we compared the single-cycle clinical pregnancy rates between 2015 to 2017 and 2018 to 2019. Next, we performed a multifactorial regression analysis to understand what changes our centre had made between the five years in terms of years. Finally, data from 2015 to 2019 were grouped as a whole and then subjected to understand exactly where the differences in clinical pregnancy rates were affecting the GnRH-ant protocol for fresh embryo transfer. Results: A total of 1,388 cycles were included from 2015 to 2017, with a clinical pregnancy rate of 51.42% (688/1388). 1,076 cycles were included from 2018 to 2019, with a clinical pregnancy rate of 57.43% (618/1076). 2018 to 2019 compared to 2015 to 2017 for first-time IVF/ICSI. There was a 6.01% increase in clinical pregnancy rate for women who had assisted conception and performed GnRH-ant protocol with fresh embryo transfer. The results of the univariate analysis conducted suggested that the factors influencing the classification of clinical pregnancy included female basal E2 base, LH base, FSH base, P base, female Gn initiation date E2 start, LH start, FSH start, P start, Gn initiation volume and number of Gn days, antagonist addition date E2 add, LH add, FSH add, P add, plate machine day E2 trigger, LH trigger, P trigger, plate machine day number of different follicles in the meridian follicles 10-14 mm, follicles 14-16 mm, follicles 16-18 mm, follicles 18mm or more. Multifactorial regression analysis after correction suggested that age, BMI, endometrial thickness on the day of transfer, number of embryos transferred and progesterone level on HCG Day were independent influencing factors for successful pregnancy with antagonist regimen and fresh embryo transfer. Conclusion: Age, BMI, endometrial thickness on the day of transfer, number of embryos transferred and progesterone levels on HCG Day were independent influences.

#129 : The Ratio of Luteal Phase Serum Progesterone and Estradiol Can be Used to Predict Pregnancy in Frozen Embryo Transfer Cycles

Background and Aims: Low serum progesterone (P) levels on day of embryo transfer (ET) and luteal phase have been associated with poorer pregnancy outcome. This study aimed to know if serum estradiol (E2) and P levels during mid and late luteal phase are related with ongoing pregnancy. Method: The serum E2 and P levels from mid luteal phase (5 days after ET) to the day of the [Formula: see text]-hCG check (11 days after ET) in both fresh and frozen embryo transfer (FET) cycles was investigated between January 2019 and December 2021. Eligible patients were reproductive aged women with a normal uterus. Single blastocyst transfer cycles were included. Estradiol valerate (2 mg/bid) was started from day 3 of cycle as hormone replacement and vaginal micronized P (400 mg/bid) was started 5 days before ET in all FET cycles. The 2-degree polynomial fitted data were analysed and logistic linear model and ROC analysis were performed to assess E2 and P4 polynomial coefficients as a predictive test for ongoing pregnancy. Results: A total of 388 patients were included. The overall pregnancy rate was 43.8% and 31.3% for FET and fresh ET, respectively. On day 5 post ET, the serum P levels correlated significantly with ongoing pregnancy and live birth rates, especially in FET cycles. The ROC curve showed that there is a significant day 5 post ET predictive value of serum P4/E2 levels for pregnancy rate, being the AUC (95% CI) = 0.596 (0.539–0.653) for the combination of both fresh and FET cycles; and 0.611 (0.548–0.674) for FET cycles, with best cut-off values of 0.079 and 0.077, respectively. Conclusion: Serum P levels in mid and late luteal phase days are associated with pregnancy outcome both in fresh and frozen ET cycles. Ongoing pregnancies can be predicted using the day 5 post ET serum P4/E2 levels.

Prognostic value of a serum β-human chorionic gonadotropin cutoff, twelve days after fresh embryo transfer, on predicting live birth among Ugandan women

Objective: This study aimed to evaluate the prognostic value of a serum β-hCG level cutoff, 12 days after embryo transfer, on predicting live births among Ugandan women. Methods: This is a retrospective cross-sectional study. Three hundred thirty-seven fresh IVF cycles with serum β-hCG ≥5 mIU/mL, at 12 days after embryo transfer, were eligible. We abstracted participant characteristics, IVF cycle characteristics, live birth, clinical pregnancy, and ongoing pregnancy data from each eligible cycle. We utilized the Youden Index metric and the maximize_boot_metric method to link serum β-hCG levels to outcome data and determine the optimal cutoff values. Results: The optimal serum β-hCG cutoff value for predicting live birth was 437.42 mIU/mL with a corresponding sensitivity and false positive rate of 72% and 31%, respectively. The cutoffs for clinical and ongoing pregnancy were 239.58 mIU/mL and 353.66 mIU/mL, respectively. These corresponded with a sensitivity of 83% and 77%, respectively, and a false positive rate of 27% and 33%, respectively. The serum β-hCG cutoff had poor discriminatory performance for predicting live births but moderate performance for predicting clinical and ongoing pregnancies. Conclusion: A single serum β-hCG 12 days after cleavage embryo transfer has poor discriminatory performance in predicting live birth, albeit performing modestly in predicting clinical pregnancy and ongoing pregnancy among Ugandan women.

#132 : Outcomes and Related Risk Factors of Heterotopic Pregnancy in IVF-ET Cycles

Background and Aims: In vitro fertilization-embryo transfer (IVF-ET) has demonstrated significant success in treating infertility, but it can also introduce complications and risks such as heterotopic pregnancy (HP), which can lead to ectopic pregnancy rupture and bleeding, potentially endangering the patient’s life and fertility. This study aims to investigate the outcomes and associated risk factors of HP following IVF-ET, providing clinical insights for HP treatment. Methods: A retrospective analysis was conducted on the clinical data, treatment, and pregnancy outcomes of patients with HP after IVF-ET admitted to First Hospital of Lanzhou University from Jan. 2012 to Dec. 2022. Statistically significant risk factors were identified and subjected to logistic regression analysis. Results: Our data revealed a HP incidence of 1.27%. Among the 66 patients with HP, 5 underwent conservative treatment (7.58%, 5/66) with a live birth rate of 25.00% (1/5). Laparoscopic surgery was performed on 61 cases (92.42%, 61/66), with a live birth rate of 77.05% (47/61). Among patients receiving laparoscopic surgery, 49.18% (30/61) had a history of pelvic surgery, 39.34% (24/61) underwent a fresh IVF cycle, and 60.66% (37/61) had a freeze-thaw cycle. The live birth rate was 83.67% (41/49) for those with a visible fetal germ and 85.37% (35/41) for those with a visible fetal heartbeat prior to surgery. Further logistic regression analysis revealed that the average diameter of the intrauterine gestational sac prior to laparoscopic surgery, the absence of a fetal germ and fetal heartbeat within the intrauterine gestational sac, and an extended duration of laparoscopic surgery were risk factors affecting pregnancy outcomes (P<0.05). Conclusion: The incidence of HP in IVF-ET is much higher than in natural conception. Laparoscopic surgery is an effective treatment for HP, which does not seem to impact the ongoing pregnancy and live birth rates of the intrauterine gestational sac. However, the patient’s pregnancy outcome can be influenced by several factors, such as the average diameter and development of the intrauterine gestational sac prior to surgery, as well as the duration of the surgery.

#312 : Outcomes for Women Who Utilise Electively Frozen Oocytes

Background and Aims: Frozen oocyte thaw (FOT) cycles are becoming increasingly common within IVF clinics in Australia, as women choose to freeze eggs and delay using those eggs until a more suitable time. Typically, Australian women freezing eggs are older than those women who have been studied in overseas FOT cycles. The aim of this study was to report outcomes of FOT cycles. Method: We performed a retrospective cohort study of 141 FOT cycles (from 129 patients) over a 10-year period from January 2010 to December 2020, at a single IVF clinic in Adelaide, Australia. We assessed the outcomes of those cycles in terms of oocyte warm survival, ICSI fertilisation rates, utilisation rates, pregnancy rates and live birth rates. Results: The average age of women undergoing FOT cycles was 36.5 ± 4.9 years. The reasons for egg freezing cycles included male factor (45.5%), elective (44.1%), religious (6.3%), fertility preservation (2.8%) and anonymous oocyte donation (1.4%). From the 143 FOT cycles, 1094 oocytes were collected; 82% of oocytes survived the warm process and 62% fertilized normally. There were 59 fresh embryo transfers (5.1% cleavage and 94.9% blastocyst, 22.0% DET and 78% SET) and 32 frozen blastocyst embryo transfers (12.5% DET and 87.5% SET). The pregnancy rate per fresh transfer was 30.0% (18/59) and per frozen transfer was 37.5% (12/32). The live birth rate per fresh transfer was 27% (16/59) and per frozen transfer was 37.5% (12/32). The live birth rate per initiated FOT cycle was 11% (16/143). Conclusion: Rates of live birth per initiated FOT cycle at our clinic was 11%, similar to the ANZARD live birth rate for all fresh cycles initiated in 2020 (10.9%). We therefore conclude that results for frozen oocytes are equivalent to fresh oocytes and can use this information when counselling patients on the outcomes of FOT cycles.

#288 : Comparison of OVOIL and OVOIL HEAVY in the Clinical IVF Laboratory on Fertilization, Blastocyst Utilization and Transfer Outcomes

Background and Aims: OVOIL HEAVY (Hv-OIL, Vitrolife) is a new synthetic oil, which compared to a paraffin oil OVOIL, has increased viscosity which may benefit handling, and provide osmolality and pH stabilisation. Being synthetically derived, Hv-OIL may reduce risk of impurities/contaminants. The manufacturer reports that Hv-OIL improves mouse and human embryo development 1 . The aim of this study was therefore to compare the effect of Hv-OIL vs OVOIL on IVF/ICSI cycle outcomes. Method: OVOIL and Hv-OIL were used across alternating fortnights for all patients in one laboratory between June 2022 and March 2023 (n=1,116 patients). Donor-recipient, egg thaw and egg freeze cycles were excluded. Embryos were cultured in G-TL media (Vitrolife) under 6.5% CO2, 5% O2 in an Embryoscope+. Results: Hv-OIL (n=554) had no effect on fertilisation rate compared to OVOIL (n=562) following either IVF (53.9% vs 55.1%) or ICSI (61.2% vs 60.5%). Utilisation rate per 2PN was similarly unaffected by oil type (51.2%± 0.01 vs 48.2%± 0.02), and this was unchanged by method of insemination. Hv-Oil had no impact on blastocyst development rate compared to OvOil (64.2 vs 61.5%), and the number of top-quality blastocysts (Gardner grade 4/5AA) per 2PN was not different (14.5% vs 16.6%). Positive hCG (46.52% vs 50.1%), fetal heart (27% vs 32%) and fetal sac (31% vs 36%) rate from fresh, single Day 5 transfers was not different between Hv-Oil (n=210 ETs) and OvOil (n=230 ETs) respectively. Osmolality of culture media in Embryoscope+ slides was not different following 7 days of incubation in either oil. Conclusion: There were no observed differences in fresh cycle outcomes with use of Hv-OIL as an oil overlay. However, the impact of Hv-OIL on live birth and FET outcomes, specific patient populations or use in different types of culture systems remains to be evaluated.

Adverse effects of type 2 diabetes mellitus on ovarian reserve and pregnancy outcomes during the assisted reproductive technology process.

To study the effect of type 2 diabetes mellitus(T2DM)on overall ovarian reserve and pregnancy outcomes during assisted reproductive technology (ART) among childbearing infertile women. Retrospective cohort study. The Reproductive Medicine Special Hospital, The First Hospital of Lanzhou University, between January 2019 and December 2022. A total of 265 infertile female patients aged 20-45 years who underwent in vitro fertilization-embryo transfer (IVF-ET), intracytoplasmic sperm injection-embryo transfer (ICSI-ET), or rescue intracytoplasmic sperm injection-embryo transfer (RICSI-ET) in the first fresh cycle. None. Serum Anti-Müllerian Hormone (AMH) levels, clinical pregnancy rate (CPR), live birth rate (LBR), and abortion rate (AR) in the T2DM group and non-T2DM group. Patients with T2DM showed statistically decreased levels of AMH compared to the non-T2DM group. During ovarian stimulation, those with T2DM required significantly higher total and initial doses of gonadotropin (GN), although they had fewer retrieved oocytes and worse pregnancy outcomes than the non-T2DM group. Multivariate logistic regression analysis adjusting for confounding factors showed that T2DM alone was an independent risk factor for CPR and LBR (adjusted odds ratio [a OR], 0.458, adjusted 95% confidence interval [CI], 0.235-0.891, P = 0.022; a OR, 0.227, 95% CI, 0.101-0.513, P<0.001; respectively), and the abortion rate in the T2DM group was 3.316 times higher than the non-T2DM group(a OR, 3.316, 95%CI, 1.248-8.811, P = 0.016). Infertile patients with T2DM have decreased ovarian reserve, and T2DM has a deleterious impact on clinical pregnancy outcomes during the ART process compared with non-T2DM infertile women. Infertile women with T2DM have decreased ovarian reserve and pregnancy outcomes during the assisted reproductive technology process compared with non-T2DM infertile women.

Effect of hyperlipidemia on the outcome of in vitro fertilization in non-obese patients with polycystic ovary syndrome.

It is little known whether hyperlipidemia alone has adverse effects on the outcome of in vitro fertilization (IVF) in patients with polycystic ovarian syndrome (PCOS). The PCOS patients with body mass index (BMI) < 30 kg/m2 were performed IVF or intracytoplasmic sperm injection treatment, including 208 fresh cycles and 127 frozen embryo transfer (FET) cycles. All the patients were divided into hyperlipidemia and control groups, and embryo quality and pregnancy outcomes between the two groups were compared. In the fresh cycles, total gonadotropin dosage in the control group was significantly lower than that in the hyperlipidemia group, and serum estradiol levels on trigger day were reversed (P < 0.05). The embryo fragment score was positively correlated with serum low-density lipoprotein level (r = 0.06, P < 0.05) and negatively with serum high-density lipoprotein (HDL) and lipoprotein A levels (r = -0.489 and -0.085, P < 0.01). Logistic regression analysis found that HDL was beneficial for clinical pregnancy (OR = 0.355, 95% CI: 0.135-0.938, P < 0.05). In the FET cycles, there were no differences in pulse index, systolic/diastolic ratio and serum estradiol and progesterone levels between the two groups, but resistance index in the hyperlipidemia group was significantly higher than that in the control group (P < 0.05). Hyperlipidemia may increase the dosage of gonadotropin and have adverse effect on the embryo quality, endometrial receptivity, and clinical outcomes of lean PCOS patients. It is recommended that the non-obese patients with hyperlipidemia and PCOS perform lipid-lowering treatment before undergoing embryo transfer.

Comparing the clinical and singleton neonatal outcomes in male infertility patients with Oligoasthenospermia, OA, or NOA following fresh ICSI-ET using different sources of sperm.

To investigate clinical and singleton newborn outcomes in fresh cycles of embryo transfer after intracytoplasmic sperm injection (ICSI-ET) with diverse sperm sources (ejaculate, epididymis, and testis) in patients with Oligoasthenospermia, obstructive azoospermia (OA) or non-obstructive azoospermia (NOA). Patients who received fresh ICSI-ET for the first time at the First Affiliated Hospital of Zhengzhou University Reproductive Medicine Center between June 2011 and June 2021 were selected for this 10-year retrospective cohort analysis. After propensity score matching, only 1630 cycles were included in the investigation of ICS-ET clinical and singleton newborn outcomes in patients with Oligoasthenospermia, OA, and NOA using sperm from diverse sperm sources. After propensity score matching, our data revealed a negligible difference in baseline and cycle parameters among groups. In patients with Oligoasthenospermia and OA, different sperm sources do not appear to influence clinical pregnancy rates and live birth rates, nor do they influence newborn outcomes, such as newborn weight, premature birth rate, and neonatal sex ratio in singleton births, except for OA patients who use epididymal sperm having higher low birth weight (LBW) rates in singleton pregnancies than those who use testicular sperm. In addition, clinical pregnancy rates, live birth rates, singleton gestation birth weights, premature birth rates, and neonatal sex ratios were similar between patients with Oligoasthenospermia, OA, and NOA using testicular sperm. Regardless of the type of male infertility (Oligoasthenospermia, OA, NOA) or sperm sources (ejaculate, epididymis, testis), a successful ICSI-ET procedure can result in similar clinical and neonatal outcomes, such as clinical pregnancy rate, live birth rate, abortion rate, neonatal birth weight and sex ratio of singleton pregnancies.

Leukemia Inhibitory Factor, Tissue Factor, Thrombomodulin, P-Selectine, D-Dimer, Thrombin Generation and Procoagulant Phospholipid Dependent Clotting Time Are Predictive for in Vitro Fertilization Outcome. the Prospective Roadmap-IVF Study

Background The link between blood hypercoagulability, endothelial cell activation and infertility or in vitro fertilization (IVF) failure is a puzzling issue. Activation of platelets, endothelial cells and blood coagulation, proinflammatory and angiogenetic potential play important role in implantation and early embryonic development. Biomarkers of cellular hypercoagulability are associated with high risk of IVF failure. Soluble Leukemia Inhibitory Factor (LIF), an interleukin 6 class cytokine expressed in the trophectoderm of the developing embryo is an important regulator in the establishment of pregnancy. Endoglin (Eng), a co-receptor for TGF-β1 and TGF-β3 is implicated in vascular complications of pregnancy and particularly in preeclampsia. Aim: The prospective longitudinal monocentric observational cohort study ROADMAP-IVF, evaluated the synergistic prognostic value of LIF and Eng with the biomarkers of cellular hypercoagulability in predicting the endometrial receptivity of fresh IVF cycles. Materials and Methods. The ROADMAP-IVF enrolled 40 women eligible for IVF with normal blood count, PT, aPTT, Fg, renal and liver function. The control group (CG) consisted of 30 healthy women with history of uncomplicated pregnancies. Exclusion criteria: Use of anticoagulant or antiplatelet agents during the last 30 days before inclusion. Known cardiovascular disease, active cancer. Active corticosteroid treatment. Primary end-point: Echographically documented pregnancy at 7 weeks from implantation. Blood was collected on day 2 (D2) from the natural cycle and 6 days after hormone treatment initiation corresponding to D8 of the cycle. Procoagulant phospholipid-dependent clotting time (PPL-ct), tissue factor (TF), thrombomodulin (TM), von Willebrand factor (vWF) and D-Dimers (DDi) were measured with assays from Diagnostica Stago (Asnieres, France). P- and E-Selectin, LIF and Eng were measured with ELISA. Thrombin generation (TG) with the TF 5 pM PPP-Reagent ® was assessed on Calibrated Automated Thrombogram (Stago, France). The cut-off values for studied biomarkers have been selected on the basis of ROC analysis. Univariate and multivariate logistic regression analysis examined the associations between the biomarkers and the study outcome. Results: 40 women were enrolled in the study. In 11 women pregnancy was confirmed with ultrasound and in 23 women no pregnancy was echographically documented. Age was not significantly different between the IVF (41 ys; range 22 - 48 ys) and the control group (40 ys; range 20 - 46 ys). At D2 and D8 the DDi and LIF were significantly higher in IVFG as compared to the CG. At D2 most of the patients had PPL-ct, DDi and MRI of TG higher than the upper normal limit (UNL). At D8 only TF was significantly increased as compared to the CG. Analytical data are presented in Table 1. Age did not correlate with the levels of the studied biomarkers. Significant correlations (p&amp;lt;0.05) were found between DDi and ETP (r=0.35); TM, TF and P-Selectin (r=0.4) at D2; TF, LIF and Eng (r=0.5) at D2 and D8; P-Selectin and PPL-ct (r=-0.4) at D2; P-Selectin and TM (r=0.4), E-Selectin (r=0.5), LIF (0.4) at D2; E-Selectin and P-Selectin (r=0.5), TF (r=0.3), and LIF (r=0.4) at D2. The ROC analysis showed that IVF failure was associate with DDi increase at D2 (AUC = 0.64); P-Selectin increase at D2(AUC = 0.57) and D8 (AUC = 0.61); TM increase at D8 (AUC = 0.61); TF increase at D8 (AUC = 0.57); LIF increase at D8 (AUC = 0.59); ETP increase at D2 (AUC = 0.67) and D8 (AUC = 0.67); Peak increase at D2 (AUC = 0.64) and D8 (AUC = 0.61). Prolongation of PPL-ct on D8 was predictive for positive pregnancy outcome(AUC 0.64). Conclusion The ROADMAP-IVF study showed that at least one out of four women eligible for IVF present biological evidence of activation of platelets, endothelial cells, blood coagulation or LIF upregulation. Hormone treatment administration does not significantly alter the proinflammatory or the hypercoagulable state. Among the studied biomarkers the levels of LIF, DDi, P-Selectine, TM and TF as well as the status of thrombin generation and PPL-ct showed a significant predictive value for the IVF outcome, particularly when measured at 6 days after hormone treatment administration. These findings will lead to the elaboration of an risk assessment model for IVF failure combining the selected biomarkers of hypercoagulability with LIF.

Evaluation of Grade 1 and Grade 2 Single Embryo Transfer Results in Fresh Cycles

Evaluation of Grade 1 and Grade 2 Single Embryo Transfer Results in Fresh Cycles

Progesterone to oocyte index is associated with live birth rate in fresh ICSI cycles of POSEIDON group 3/4 patients

Progesterone to oocyte index is associated with live birth rate in fresh ICSI cycles of POSEIDON group 3/4 patients

Body mass index impacts ectopic pregnancy during in vitro fertilization: an analysis of 42,362 clinical pregnancy cycles

PurposeThis large, single-center, retrospective cohort study was aimed to explore the effect of female body mass index (BMI) on ectopic pregnancy (EP) following fresh and frozen-thawed embryo transfers (ET).MethodsA total of 27,600 pregnancies after fresh ET and 14,762 pregnancies after frozen-thawed ET were included between January 2010 to June 2022. Women were divided into three groups based on BMI according to the Working Group on Obesity in China (WGOC), International Life Sciences Institute (ILSI): underweight (BMI < 18.5 kg/m2), normal weight (BMI, 18.5–23.9 kg/m2), and overweight or obesity (≥ 24 kg/m2). Compare EP rates among BMI categories in fresh and frozen-thawed ET cycles respectively. Multivariate logistic regression analyses were used to investigate the association between female BMI and EP.ResultsThe overall EP rates in fresh, and frozen thawed transfer cycles were 2.43% (672/27,600) and 2.82% (417/14,762), respectively. In fresh ET cycles, underweight women yielded a significantly higher EP rate than those with normal and excess weight (3.29% vs. 2.29% vs. 2.54%, P = 0.029). But EP rates did not differ among the three BMI groups (2.72% vs. 2.76% vs. 2.96%, P = 0.782) in frozen-thawed ET cycles. In fresh ET cycles, after adjusting for potential confounding factors, no significant association was found between female BMI and EP occurrence (adjusted OR: 0.98, 95% CI 0.70–1.37, P = 0.894, for BMI 18.5–23.9 kg/m2; adjusted OR: 0.89, 95% CI 0.75–1.06, P = 0.205, for BMI ≥ 24 kg/m2. Reference = BMI < 18.5 kg/m2).Conclusion(s)Female BMI did not affect the occurrence of ectopic pregnancy in either fresh or frozen-thawed embryo transfer cycles.

Comparing reproductive outcomes between conventional in vitro fertilization and nonindicated intracytoplasmic sperm injection in autologous embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Study

ObjectiveTo compare clinical outcomes between non-indicated ICSI and conventional insemination. DesignAutologous cycles performed at SART member clinics from 2014-2017 were identified, excluding frozen oocyte cycles. Outcomes conventional insemination (IVF) or non-indicated ICSI were analyzed separately for fresh, frozen-thawed pre-implantation genetic testing (PGT) and frozen-thawed non-PGT cycles. Subjects187,520 patients underwent 318,930 cycles, 57,516 (18.0%) using conventional IVF and 261,414 ICSI (82.0%). ExposureICSI, with or without indications [male factor, prior fertilization failure or any PGT (2012 recommendations)/single-gene PGT (2020 recommendations)]. Main Outcome MeasuresOdds ratios (ORs) for live birth rates and clinical pregnancy rates were calculated after multivariable adjustment for maternal age, BMI, infertility etiologies, prior IVF births and number oocytes retrieved. ResultsICSI was indicated in 151,627 (58.0%) of cycles according to 2012 ASRM Practice Committee recommendations, and 108,895 (41.7%) according to 2020 recommendations.In multivariable models, non-indicated ICSI among fresh cycles was associated with reduced odds of completing a blastocyst-stage transfer (OR 0.72, 95% CI (0.7, 0.75), p<0.001), resulting in reduced odds of live birth (OR 0.80, 95% CI (0.78,0.83), p<0.001). Among completed fresh transfers, clinical pregnancy and live birth rates were comparable between non-indicated ICSI and IVF.Non-indicated ICSI in frozen-thawed cycles with PGT and without PGT was associated with comparable live birth and clinical pregnancy rates to IVF in multivariable models. ConclusionNon-indicated ICSI was associated with reduced blastocyst availability in fresh cycles compared with IVF, leading to lower live birth rates. Outcomes from completed transfers were clinically comparable.

Effect of growth hormone administration on ameliorating pregnancy outcome in women with advanced maternal age and exploration of its optimized utilization.

Age-related fertility decay is a great challenge for clinicians. Growth hormone (GH) supplementation has been studied as an adjuvant since late 1980s. However, it has not come to a consensus on the GH administration due to the ambiguous efficacy among studies with different enrolled population and dosage regime. A self-controlled retrospective study was conducted on women with advanced maternal age who underwent at least a previous cycle without GH (GH-) and a subsequent cycle with GH co-treatment (GH+). The ovarian stimulation parameters and outcomes were compared between the two cycles and logistical analysis was applied to further explore the association between GH administration protocol as well as other clinical parameters and cumulative live birth in GH+cycle. A total of 150 women aged 35-43 were included. The number of oocytes retrieved, MII oocytes, 2PNs, transferrable embryos and good-quality embryos in GH+ significantly increased (p < 0.001). The proportion of cycles with no transferrable embryos was significantly reduced in GH+ cycle compared with previous GH- cycle (3 vs. 32; p < 0.001). GH co-treatment cycles showed significantly higher clinical pregnancy rates (43.75% vs. 6.06%; 38.35% vs. 12.04%, p < 0.001), live birth rates (29.17% vs. 0; 27.07% vs. 0, p < 0.001) in both fresh and frozen-thawed embryo transfer cycle. Cumulative live birth rate of the GH+ cycle reached 33.33%. Use of GH prior to Gn stimulation and lasting until the hCG day seemed to achieve a higher successful live birth rate (OR 2.312, 95%CI 1.074-5.163, p=0.032). GH supplementation could ameliorate pregnancy outcome in women with advanced maternal age. Dosage regimen of long-term pretreatment prior to Gn stimulation (4 IU every other day) and 4 IU per day until hCG day may of greater efficacy compared with concurrent administration with Gn. Additionally, it's worthy of exploring whether an individualized dosage regimen based on the IGF or IGFBP level of patient would be more reasonable and effective. More well-designed prospective trials with large sample size and fundamental experiments on the mechanism are required to testify findings above.

Initial β-hCG levels and 2-day-later increase rates effectively predict pregnancy outcomes in single blastocyst transfer in frozen-thawed or fresh cycles: A retrospective cohort study.

To investigate whether the initial beta-human chorionic gonadotropin (β-hCG) levels and their rate of increase differ after single fresh and frozen blastocyst transfers, and whether these values effectively predict pregnancy outcomes. This retrospective cohort study was conducted at the Sisli Memorial Hospital, assisted reproductive technology, and Reproductive Genetics Center in Istanbul, Turkey, between January 2016 and January 2022. Three thousand two hundred thirty-eight single blastocyst transfers with positive pregnancy test results were evaluated. Of these, 738 were fresh transfer cycles and 2500 were frozen-thawed embryo transfer (FET) cycles. β-hCG test results from 9 days after fresh and FET cycles were compared between the groups with biochemical pregnancy, early pregnancy loss, and live birth outcomes. The threshold values were determined for each pregnancy outcome. The rate of increase between the first and second β-hCG tests performed 2 days apart was determined for each pregnancy outcome. Finally, the listed values were compared between the FET and fresh cycle. Mean baseline β-hCG levels were significantly higher in FET cycles than in fresh cycles, regardless of pregnancy outcomes (P < .005). Baseline β-hCG levels were higher in fresh cycles with live births (171.76 ± 109.64 IU/L) compared to biochemical and clinical pregnancy losses (50.37 ± 24.31 and 114.86 ± 72.42, respectively) (P < .001). Live births in FET cycles resulted in higher baseline β-hCG levels (193.57 ± 100.38 IU/L) compared to biochemical and clinical pregnancy loss groups (68.41 ± 51.85 and 149.29 ± 96.99 IU/L, respectively) (P < .001). The β-hCG threshold for live birth for fresh cycles was 116.5 IU/L (sensitivity 80%, specificity 70%, positive predictive value 90%, negative predictive value 54%) and 131.5 IU/L for FET cycles (sensitivity 71%, specificity 68%, positive predictive value 87%, negative predictive value 50%). The percentage of the area under the curve for single fresh blastocyst transfers was 0.81 and 0.76 for frozen transfers. The rate of increase in β-hCG was similar in fresh and FET cycles. Initial β-hCG levels and 2-day increases are effective parameters for diagnosing pregnancy in fresh and FET cycles. The initial β-hCG level was significantly higher in the FET cycles than in the fresh cycles. Predicting outcomes earlier helps clinicians to manage and follow high-risk pregnancies.

ART in Europe, 2019: results generated from European registries by ESHRE†.

What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2019 as compared to previous years? The 23rd ESHRE report highlights the rising ART treatment cycles and children born, alongside a decline in twin deliveries owing to decreasing multiple embryo transfers; fresh IVF or ICSI cycles exhibited higher delivery rates, whereas frozen embryo transfers (FET) showed higher pregnancy rates (PRs), and reported IUI cycles decreased while maintaining stable outcomes. ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF-Monitoring (EIM) Consortium since 1997 and reported in a total of 22 manuscripts published in Human Reproduction and Human Reproduction Open. Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between 1 January and 31 December 2019 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in one of the 44 countries that are members of the EIM Consortium. Overall, 1487 clinics offering ART services in 40 countries reported, for the second time, a total of more than 1 million (1077813) treatment cycles, including 160782 with IVF, 427980 with ICSI, 335744 with FET, 64089 with preimplantation genetic testing (PGT), 82373 with egg donation (ED), 546 with IVM of oocytes, and 6299 cycles with frozen oocyte replacement (FOR). A total of 1169 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 147711) or donor semen (IUI-D; n = 51651) in 33 and 24 countries, respectively. Eighteen countries reported 24139 interventions in pre- and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking. In 21 countries (21 in 2018) in which all ART clinics reported to the registry 476760 treatment cycles were registered for a total population of approximately 300 million inhabitants, allowing the best estimate of a mean of 1581 cycles performed per million inhabitants (range: 437-3621). Among the reporting countries, for IVF the clinical PRs per aspiration slightly decreased while they remained similar per transfer compared to 2018 (21.8% and 34.6% versus 25.5% and 34.1%, respectively). In ICSI, the corresponding PRs showed similar trends compared to 2018 (20.2% and 33.5%, versus 22.5% and 32.1%) When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.5% (28.8% in 2018) and 26.2% (27.3% in 2018) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was at 35.1% (versus 33.4% in 2018), and with embryos originating from donated eggs at 43.0% (41.8% in 2018). After ED, the PR per fresh embryo transfer was 50.5% (49.6% in 2018) and per FOR 44.8% (44.9% in 2018). In IVF and ICSI together, the trend toward the transfer of fewer embryos continues with the transfer of 1, 2, 3, and ≥4 embryos in 55.4%, 39.9%, 2.6%, and 0.2% of all treatments, respectively (corresponding to 50.7%, 45.1%, 3.9%, and 0.3% in 2018). This resulted in a reduced proportion of twin delivery rates (DRs) of 11.9% (12.4% in 2018) and a similar triplet DR of 0.3%. Treatments with FET in 2019 resulted in twin and triplet DR of 8.9% and 0.1%, respectively (versus 9.4% and 0.1% in 2018). After IUI, the DRs remained similar at 8.7% after IUI-H (8.8% in 2018) and at 12.1% after IUI-D (12.6% in 2018). Twin and triplet DRs after IUI-H were 8.7% and 0.4% (in 2018: 8.4% and 0.3%) and 6.2% and 0.2% after IUI-D (in 2018: 6.4% and 0.2%), respectively. Eighteen countries (16 in 2018) provided data on FP in a total number of 24139 interventions (20994 in 2018). Cryopreservation of ejaculated sperm (n = 11592 versus n = 10503 in 2018) and cryopreservation of oocytes (n = 10784 versus n = 9123 in 2018) were most frequently reported. Caution with the interpretation of results should remain as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. The 23rd ESHRE data collection on ART, IUI, and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts toward optimization of both the collection and the reporting, from the perspective of improving surveillance and vigilance in the field of reproductive medicine, are awaited. The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

Effective protection: the embryonic development and clinical outcomes of emergency vitrification of 1246 oocytes and Day 0-Day 5 embryos in a natural disaster.

Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. N/A.

The Comparison of Two Whole-Genome Amplification Approaches for Noninvasive Preimplantation Genetic Testing (ni-PGT) and the Application Scenario of ni-PGT during the Fresh Cycle

Recently, noninvasive preimplantation genetic testing (ni-PGT) using degenerate oligonucleotide primer PCR (DOP-PCR) and multiple annealing and looping-based amplification cycle (MALBAC)-based whole-genome amplification (WGA) methods has demonstrated predictable results in embryo testing. However, a considerable heterogeneity of results has been reported in numerous studies on these two WGA methods. Our aim was to evaluate the current WGA method for ni-PGT while further clarifying the applicable scenarios of ni-PGT in the fresh cycle. A total of 173 embryos were tested with trophectoderm biopsy and ni-PGT. In the whole preimplantation genetic testing, the clinical concordance rates of the detection results of DOP-PCR and MALBAC with the corresponding trophectoderm biopsy results were 64.12% (84/131) and 68.99% (89/129), respectively (P=0.405). However, in the detection of abnormal embryos, the detection efficiency of ni-PGT is significantly improved [MALBAC: 96.55% versus 68.99% (P<0.001); and DOP-PCR: 89.09% versus 64.12% (P<0.001)]. In addition, the diagnostic efficiency of ni-PGT in low-quality blastocysts was significantly higher than that in high-quality blastocysts [MALBAC: 95.24% versus 51.85% (P=0.001); and DOP-PCR: 91.30% versus 48.15% (P=0.001)]. These results contribute to further understanding ni-PGT and to clarifying its application scenario in the fresh cycle.

Ultrasonographic endometrial classification in In Vitro Fertilization: a new approach

In the context of In Vitro Fertilization (IVF), we introduce an innovative approach for assessing the endometrium via transvaginal ultrasound. Diverging from previous studies that centered on the comprehensive thickness and pattern of the endometrium, our methodology scrutinizes both the absolute and relative dimensions of its external layers, relative to the aforementioned factors. Our findings reveal a significant departure from conventional paradigms. Specifically, when the external layers of the endometrium achieve or exceed 50% of the total endometrial composition in a trilaminar configuration, a substantial enhancement in pregnancy rates is manifest. Conversely, when the proportion of external layers diminishes below 50% of endometrial thickness, a marked decline in pregnancy rates is evident. Furthermore, within both fresh and frozen embryo transfer cycles, the presence of slender external layers corresponds to a notable absence of pregnancies. Importantly, our study underscores that pregnancies did not occur when the total endometrial thickness measured below 7mm. The results gleaned from our comprehensive analysis, encompassing a cohort of 271 subjects, warrant replication and validation by fellow experts in the field. By corroborating these outcomes and embracing the novel classification of endometrial dynamics in IVF, clinicians and scientists can refine and optimize patient care in assisted reproductive technologies.