Perinatal outcomes of singleton live births after preimplantation genetic testing during single frozen-thawed blastocyst transfer cycles: a propensity score-matched study.

OBJECTIVE: To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton pregnancy. DESIGN: A retrospective cohort study. SETTING: A university-affiliated fertility center. PATIENT(S): This cohort study included singleton live births resulting from PGT (n = 232) and IVF/ICSI singleton pregnancies (n = 2,829) with single frozen-thawed blastocyst transfer. Multiple baseline covariates were used for propensity score matching, yielding 214 PGT singleton pregnancies matched to 617 IVF/ICSI singleton pregnancies. INTERVENTION(S): Trophectoderm biopsy. MAIN OUTCOME MEASURE(S): The primary outcome was gestational hypertension, and various clinical perinatal secondary outcomes related to maternal and neonatal health were measured. RESULT(S): Compared with IVF/ICSI singleton pregnancy, PGT singleton pregnancy was associated with a significantly higher risk of gestational hypertension (adjusted odds ratio, 2.58; 95% confidence interval, 1.32, 5.05). In the matched sample, the risk of gestational hypertension remained higher with PGT singleton pregnancy (odds ratio, 2.33; 95% confidence interval, 1.04, 5.22) than with IVF/ICSI singleton pregnancy. No statistical differences were noted in any other measured outcomes between the groups. CONCLUSION(S): The perinatal outcomes of PGT and IVF/ICSI singleton pregnancies were similar except for the observed potentially higher risk of gestational hypertension with PGT singleton pregnancy. However, because the data on PGT singleton pregnancies are limited, this conclusion warrants further investigation.

Defining recurrent implantation failure: a profusion of confusion or simply an illusion?

Recurrent implantation failure (RIF) is a poorly defined clinical scenario marked by failure to achieve pregnancy after multiple embryo transfers. The causes and definitions of implantation failure are heterogeneous, posing limitations on study design as well as the interpretation and application of findings. Recent studies suggest a novel, personalized approach to defining RIF. Here, we review the implantation physiology and definitions of the implantation rate, failure, and RIF.

A review of the pathophysiology of recurrent implantation failure.

Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment.

Endometrial thickness changes after progesterone administration do not affect the pregnancy outcomes of frozen-thawed euploid blastocyst transfer: a retrospective cohort study.

OBJECTIVE: To evaluate whether the change in endometrial thickness from progesterone administration day to transfer day is related to pregnancy outcomes in single frozen-thawed euploid blastocyst transfer cycles. DESIGN: Observational cohort study. SETTING: Single reproductive medical center. PATIENT(S): All patients were transferred with a single biopsied euploid blastocyst, and their endometrium was prepared with hormone replacement therapy (HRT). INTERVENTION(S): The endometrial thickness on the day of blastocyst transfer and progesterone administration was measured by transvaginal ultrasound, and the difference between them and the change ratio were calculated. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates and live birth rates. RESULT(S): Endometrial ultrasound images of 508 euploid blastocyst transfer cycles using HRT were evaluated by transvaginal ultrasound. Overall, pregnancy outcomes were comparable in different groups of endometrial thickness changes. The results of multiple logistic regression showed that the clinical pregnancy rate and live birth rate did not significantly increase with the increase in endometrial thickness change ratios (per 10%) in the fully adjusted model as a continuous variable. In the adjustment model as a categorical variable, there was no statistical difference in pregnancy outcomes among the groups with changes in endometrial thickness. Interaction analysis showed that after adjusting for confounders, there was no statistically significant interaction between the endometrial thickness change ratio and pregnancy outcomes in all subgroups. CONCLUSION(S): In the euploid blastocyst transfer cycle of preparing the endometrium with HRT, the endometrial thickness change ratio after progesterone administration was not related to pregnancy outcomes.

Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing FET. INTERVENTION(S): We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate. RESULT(S): Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs. CONCLUSION(S): Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET. PROSPERO NUMBER: CRD42019157071.

Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study.

The sex ratio at birth is defined as the secondary sex ratio (SSR). Ovarian hyperstimulation syndrome (OHSS) is a serious and iatrogenic complication associated with controlled ovarian stimulation (COS) during assisted reproductive technology (ART) treatments. It has been hypothesized that the human SSR is partially controlled by parental hormone levels around the time of conception. Given the aberrant hormonal profiles observed in patients with OHSS, this retrospective study was designed to evaluate the impact of OHSS on the SSR. In this study, all included patients were divided into 3 groups: non-OHSS (n=2777), mild OHSS (n=644), and moderate OHSS (n=334). Our results showed that the overall SSR for the study population was 1.033. The SSR was significantly increased in patients with moderate OHSS (1.336) compared to non-OHSS patients (1.002) (p=0.048). Subgroup analyses showed that increases in the SSR in patients with moderate OHSS were observed in the IVF group (1.323 vs 1.052; p=0.043), but not in the ICSI groups (1.021 vs 0.866; p=0.732). In addition, the elevated serum estradiol (E2) and progesterone (P4) levels in OHSS patients were not associated with SSR. In this study, for the first time, we report that a high SSR is associated with OHSS in patients who received fresh IVF treatments. The increases in SSR in OHSS patients are not attributed to the high serum E2 and P4 levels. Our findings may make both ART clinicians and patients more aware of the influences of ART treatments on the SSR and allow clinicians to counsel patients more appropriately.

Oocyte competence is independent of the ovulation trigger adopted: a large observational study in a setting that entails vitrified-warmed single euploid blastocyst transfer.

PURPOSE: To assess whether the GnRH-agonist or urinary-hCG ovulation triggers affect oocyte competence in a setting entailing vitrified-warmed euploid blastocyst transfer. METHODS: Observational study (April 2013-July 2018) including 2104 patients (1015 and 1089 in the GnRH-a and u-hCG group, respectively) collecting ≥1 cumulus-oocyte-complex (COC) and undergoing ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing, and vitrified-warmed transfers at a private clinic. The primary outcome measure was the euploid-blastocyst-rate per inseminated oocytes. The secondary outcome measure was the maturation-rate per COCs. Also, the live-birth-rate (LBR) per transfer and the cumulative-live-birth-delivery-rate (CLBdR) among completed cycles were investigated. All data were adjusted for confounders. RESULTS: The generalized-linear-model adjusted for maternal age highlighted no difference in the mean euploid-blastocyst-rate per inseminated oocytes in either group. The LBR per transfer was similar: 44% (n=403/915) and 46% (n=280/608) in GnRH-a and hCG, respectively. On the other hand, a difference was reported regarding the CLBdR per oocyte retrieval among completed cycles, with 42% (n=374/898) and 25% (n=258/1034) in the GnRh-a and u-hCG groups, respectively. Nevertheless, this variance was due to a lower maternal age and higher number of inseminated oocytes in the GnRH-a group, and not imputable to the ovulation trigger itself (multivariate-OR=1.3, 95%CI: 0.9-1.6, adjusted p-value=0.1). CONCLUSION: GnRH-a trigger is a valid alternative to u-hCG in freeze-all cycles, not only for patients at high risk for OHSS. Such strategy might increase the safety and flexibility of controlled-ovarian-stimulation with no impact on oocyte competence and IVF efficacy.

Blastocyst conversion rate and ploidy in patients with structural rearrangements.

OBJECTIVE: The primary objective of this study was to test the hypotheses that compared to IVF cycles undergoing preimplantation genetic testing for aneuploidy (PGT-A) with or without testing for monogenic disorders (PGT-M), IVF cycles undergoing PGT for structural rearrangements (PGT-SR) will have (1) a poorer blastocyst conversion rate and (2) fewer usable blastocysts available for transfer. Secondarily, the study aimed to compare pregnancy outcomes among PGT groups. PATIENTS: Retrospective cohort study including cycles started from January 1, 2012, to March 30, 2020, with the intent of pursuing PGT-A, PGT-A with PGT-M, and PGT-SR, with trophectoderm biopsy on days 5 or 6. RESULTS: A total of 658 women underwent 902 cycles, including 607 PGT-A, 216 PGT-A&M, and 79 PGT-SR cycles. When compared with the blastocyst conversion rate for the PGT-A group (59.4%), and after adjustment for patient age, total number of mature oocytes, BMI, and ICSI, there were no significant differences for either the PGT-A&M (69.7%, aRR 1.03, 95% CI 0.96-1.10) or PGT-SR (63.2%, aRR1.04, 95% CI 0.96-1.13) groups. Compared to the PGT-A group, the proportion of usable blastocysts was statistically significantly lower in the PGT-SR group: 35.1% versus 24.4% (aRR 0.57, 95% CI 0.46-0.71) and the PGT-A&M group: 35.1% versus 31.5% (aRR 0.68, 95% CI 0.58-0.81). Implantation, pregnancy, and miscarriage rates were equivalent for all groups. CONCLUSION: Patients with structural rearrangements have similar blastocyst development but significantly fewer usable blastocysts available for transfer compared to PGT-A testers. Nevertheless, with the transfer of a usable embryo, PGT-SR testers perform as well as those testing for PGT-A.

Trophectoderm biopsy protocols may impact the rate of mosaic blastocysts in cycles with pre-implantation genetic testing for aneuploidy.

PURPOSE: This study aimed to analyze the impact of different biopsy protocols on the rate of mosaic blastocysts. METHODS: This is a retrospective cohort study which included 115 cycles with pre-implantation genetic testing for aneuploidy (PGT-A). Two groups were allocated based on the biopsy protocols: method 1 group, the zona pellucida (ZP) was drilled on day 3 embryos followed by trophectoderm (TE) biopsy; and method 2 group, the ZP was opened on day 5 or 6 blastocysts followed by TE biopsy. All biopsy samples were assessed using next-generation sequencing (NGS) at a single reference laboratory. The euploid, aneuploid, and mosaic blastocyst rates and clinical outcomes were compared. RESULTS: The mosaicism rate in the method 1 group was 19.58%, significantly higher than the method 2 group (8.12%; P < 0.05). No statistically significant difference was observed in euploid, aneuploid blastocyst rates, and clinical pregnancy rates between the two groups. Logistic regression analysis indicated that the biopsy protocols were independently associated with the mosaicism rates among all the variables. CONCLUSIONS: The present study showed that different biopsy protocols may have an impact on the mosaic blastocyst rate. ZP opening on day 3 combined with TE biopsy might increase the incidence of mosaic blastocysts.

Routine endometrial receptivity array in first embryo transfer cycles does not improve live birth rate.

OBJECTIVE: To compare the live birth rate between patients who undergo personalized embryo transfer (pET) after endometrial receptivity array (ERA) versus frozen embryo transfer (FET) with standard timing in first single euploid FET cycles. To report the rate of displacement of the window of implantation (WOI) in an infertile population without a history of implantation failure. DESIGN: Prospective cohort study of patients who underwent their first single euploid programmed FET. SETTING: Private fertility clinic. PATIENT(S): Patients who underwent first autologous single euploid programmed FET between January 2018 and April 2019. INTERVENTION(S): Endometrial biopsy with ERA followed by pET as indicated. MAIN OUTCOME MEASURE(S): Live birth rate and rate of receptive and nonreceptive ERA. RESULT(S): A total of 228 single euploid FET cycles were included in our analysis. Of those, 147 (64.5%) were ERA/pET cycles, and 81 (35.5%) were standard timing FET cycles. Endometrial receptivity array was receptive in 60/147 (40.8%) and nonreceptive in 87/147 (59.2%) patients. Nonreceptive ERAs were prereceptive in 93.1% of cases. The live birth rate did not differ between patients who underwent FET with standard timing and patients who underwent ERA/pET, 45/81 (56.6%) and 83/147 (56.5%), respectively. CONCLUSION(S): Our data do not support the routine use of ERA in an unselected patient population undergoing first autologous single euploid programmed embryo transfer.

Detection of early placental hormone production in embryo transfer cycles lacking a corpus luteum.

PURPOSE: This study sought to identify the initiation of placental hormonal production as defined by the production of endogenous estradiol (E2) and progesterone (P4) in a cohort of patients undergoing programmed endometrial preparation cycles with single embryo transfers resulting in live-born singletons. METHODS: In this retrospective cohort study, patients undergoing either programmed frozen-thawed embryo transfer (FET) with autologous oocytes or donor egg recipient (DER) cycles with fresh embryos were screened for inclusion. Only patients who underwent a single embryo transfer, had a single gestational sac, and a resultant live-born singleton were included. All patients were treated with E2 patches and intramuscular progesterone injections. Main outcome measures were serial E2 and P4, with median values calculated for cycle days 28 (baseline), or 4w0d gestational age (GA), through 60, or 8w4d GA. The baseline cycle day (CD) 28 median value was compared to each daily median cycle day value using the Wilcoxon signed rank test. RESULTS: A total of 696 patients, 569 using autologous oocytes in programmed FET cycles and 127 using fresh donor oocytes, from 4/2013 to 4/2019 met inclusion criteria. Serum E2 and P4 levels stayed consistent initially and then began to increase daily. Compared to baseline CD 28 E2 (415 pg/mL), the serum E2 was significantly elevated at 542 pg/mL (P < 0.001) beginning on CD 36 (5w1d GA). With respect to baseline CD 28 P4 (28.1 ng/mL), beginning on CD 48 (6w6d GA), the serum P4 was significantly elevated at 31.6 ng/mL (P < 0.001). CONCLUSION: These results demonstrate that endogenous placental estradiol and progesterone production may occur by CD 36 and CD 48, respectively, earlier than traditionally thought.

Analysis of Biochemical and Clinical Pregnancy Loss Between Frozen-Thawed Embryo Transfer of Blastocysts and Day 3 Cleavage Embryos in Young Women: A Comprehensive Comparison.

Background: To determine whether the embryo developmental stage affects biochemical or clinical pregnancy loss in young women undergoing frozen-thawed embryo transfer (FET) and to investigate the underlying mechanism. Methods: This was a retrospective study including a total of 18,34 ß-HCG (human chorionic gonadotropin)-positive FET cycles. According to the morphological appearance (MA) of transferred blastocysts, FET cycles with blastocysts were divided into two groups: Group A: morphologically good (MG) blastocysts only, and Group B: at least one morphologically non-good (MNG) blastocyst. FET cycles with day 3 cleavage embryos were assigned as Group C. Biochemical and clinical pregnancy loss were the main outcome measures. Results: We predicted 78% in vivo-formed MG and 53.9% in vivo-formed day 5 blastocysts in Group C. (a) Including cases in Group A and Group B for binary logistic regression, we showed that Group B and day 6 blastocysts had significantly higher rates of BPL and CPL than Group A and day 5 blastocysts, respectively. (b) Including cases in Group A, Group B, and Group C for binary logistic regression, we showed that Group C had a significantly higher rate of BPL than Group A and day 5 blastocysts and a similar rate of BPL as Group B and day 6 blastocysts. Group C had a higher rate of CPL than Group A (p=0.071) and day 5 blastocysts (p=0.039), and a lower rate of CPL than Group B (p=0.199) and day 6 blastocysts (p=0.234). Conclusions: (1) MA and days of usable blastocysts could serve as independent factors affecting the occurrence of BPL and CPL. (2) Transfer of day 3 cleavage embryos may produce "unusable blastocysts" in vivo, which significantly increased the rate of BPL. (3) The rate of CPL resulting from the transfer of day 3 embryos may depend on the rate of in vivo-formed MG or day 5 blastocysts. Our study indicated that the difference in the BPL or CPL between transfer of blastocysts and day 3 cleavage embryos may largely depend on the quality of embryos transferred.

Successful implantation is associated with a transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy.

OBJECTIVE: To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. DESIGN: Prospective, observational, and longitudinal study. SETTING: University-affiliated hospital. PATIENT(S): Forty-seven women with infertility who were undergoing single day-5 blastocyst transfer were recruited. INTERVENTION(S): This prospective observational and longitudinal study on 47 women with infertility was performed in an in vitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. MAIN OUTCOME MEASURE(S): Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, IL-10, IL-12, IL-13, IL-17, IL-18, and IL-22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-ß1) was measured using commercial enzyme-linked immunosorbent assay kits. RESULT(S): The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL-17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL-10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-ß1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL-17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. CONCLUSION(S): Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL-17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL-10 and TGF-ß1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed.

Neonatal outcomes in women with polycystic ovary syndrome after frozen-thawed embryo transfer.

OBJECTIVE: To compare the risk of adverse neonatal outcomes after frozen embryo transfer (FET) among women with polycystic ovary syndrome (PCOS) with those among women without PCOS. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): In this study, we included 1,167 singletons born to mothers with PCOS and 9,995 singletons born to mothers without PCOS after FET during the period from January 1, 2007, to December 31, 2019. INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Adverse neonatal outcomes including preterm birth, low birth weight, high birth weight, small for gestational age (SGA), and large for gestational age. RESULT(S): The odds of preterm birth were significantly higher among infants from mothers with PCOS compared with those from mothers without PCOS. The odds of low birth weight and SGA were lower in mothers with PCOS compared with mothers without PCOS in the overall analysis, but the differences in low birth weight and SGA between mothers with and without PCOS did not exist in the subgroup analysis with a normal BMI population. CONCLUSION(S): The diagnosis of PCOS was independently associated with increased odds of preterm birth among women with singleton pregnancies by FET. In addition, decreased odds of low birth weight and SGA were observed among patients with PCOS, but the increased odds were not observed in the subset analysis of patients with PCOS with normal BMI.

Development and clinical application of a preimplantation genetic testing for monogenic disease (PGT-M) for beta thalassemia in Vietnam.

PURPOSE: The purpose of this research is to study the clinical outcomes using a next-generation sequencing-based protocol allowing for simultaneous testing of mutations in the beta thalassemia (HBB) gene, including single nucleotide polymorphism (SNP) markers for PGT-M along with low-pass whole genome analysis of chromosome aneuploidies for PGT-A. METHODS: A combined PGT-M (thalassemia) plus PGT-A system was developed for patients undergoing IVF in Vietnam. Here we developed a system for testing numerous thalassemia mutations plus SNP-based testing for backup mutation analysis and contamination control using next-generation sequencing (NGS). Low -pass next-generation sequencing was used to assess aneuploidy in some of the clinical PGT cases. Patients underwent IVF followed by embryo biopsy at the blastocyst stage for combined PGT-A/M. RESULTS: Two cases have completed the entire process including transfer of embryos, while a further nine cases have completed the IVF and PGT-M/A analysis but have not completed embryo transfer. In the two cases with embryo transfer, both patients achieved pregnancy with an unaffected, euploid embryo confirmed through prenatal diagnosis. In the further nine cases, 39 embryos were biopsied and all passed QC for amplification. There were 8 unaffected embryos, 31 carrier embryos, and 11 affected embryos. A subset of 24 embryos also had PGT-A analysis with 22 euploid embryos and 2 aneuploid embryos. CONCLUSIONS: Here we report the development and clinical application of a combined PGT-M for HBB and PGT-A for gross chromosome aneuploidies from 11 patients with detailed laboratory findings along with 2 cases that have completed embryo transfer.

Trophectoderm biopsy reduces the level of serum ß-human chorionic gonadotropin in early pregnancy.

OBJECTIVE: To assess whether trophectoderm biopsy has any impact on the level of serum ß-human chorionic gonadotropin (ß-hCG) in early pregnancies. DESIGN: Retrospective cohort study. SETTING: University-affiliated reproductive medical center. PATIENT(S): Three hundred and eighty-three women undergoing 396 frozen embryo transfer (FET) cycles with preimplantation genetic testing (PGT), and 353 women undergoing 465 FET cycles with in vitro fertilization or intracytoplasmic sperm injection, all women having positive serum ß-hCG results on the 12th day after blastocysts transfers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum ß-hCG levels on the 12th day after warmed blastocyst transfer and perinatal outcomes of clinical pregnancy. RESULTS: The diagnostic threshold of serum ß-hCG levels on the 12th day after FET for prediction of a live birth was 368.55 mIU/mL with an area under the curve of 0.791 (0.729∼0.853) in the biopsy group, which was lower than the 411.45 mIU/mL in the control group. The average level of serum ß-hCG in the biopsy group with clinical pregnancies was statistically significantly lower than that of the control group: 703.10 (569.63) versus 809.20 (582.00), respectively. No statistically significant differences in perinatal outcomes, including gestational age, hypertensive disorder in pregnancy, and neonatal malformation, were found between the two groups. CONCLUSION(S): Trophectoderm biopsy may reduce the level of serum ß-hCG in early pregnancies (the 12th day after embryo transfer), but no increased risk was found of adverse perinatal outcomes after trophectoderm biopsy.

Natural cycle frozen-thawed embryo transfer in young women with regular menstrual cycles increases the live-birth rates compared with hormone replacement treatment: a retrospective cohort study.

OBJECTIVE: To determine the optimal endometrial preparation protocols of frozen-thawed embryo transfer (FET) in young women with regular menstrual cycles. DESIGN: Retrospective cohort study. SETTING: Public fertility center. PATIENT(S): Infertile women with regular menstrual cycles undergoing FET. INTERVENTION(S): Natural cycle (NC) treatment for patients with proven ovulation in previous cycles or who refused medication (n = 308), or hormone treatment (HT) for patients who could not be frequently monitored (n = 1,538). MAIN OUTCOME MEASURE(S): Live-birth rates. RESULT(S): The live-birth rates were 61.73% in the NC group and 55.11% in the HT group. The effect size of the endometrial preparation on live-birth rates was evaluated in prespecified and exploratory subgroups in each subgroup, and multivariable logistic regression analysis was used to determine which variables could be independently associated with the live-birth rate. The HT patients had a lower chance of live birth in all subgroups: endometrial thickness on the day of progesterone administration, triple-line endometrial pattern, female age at embryo transfer, fertilization type, and protocol in the fresh cycle. Multivariable analysis showed NC to be associated with an increased likelihood of live birth compared with HT. CONCLUSION(S): Natural cycle treatment has a higher chance of live birth than HT for endometrial preparation in young women with regular menstrual cycles.

Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization-intracytoplasmic sperm injection and embryo transfer cycles.

OBJECTIVE: To investigate whether endometrial thickness (EMT) is associated with adverse obstetric and neonatal outcomes in fresh in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. DESIGN: Retrospective cohort study. SETTING: University-based reproductive medical center. PATIENT(S): Women under the age of 42 years who underwent IVF/ICSI treatment and received fresh ET in our unit from January 2017 to December 2018, resulting in a live singleton birth. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF/ICSI; fresh ET. MAIN OUTCOME MEASURE(S): Birth weight, gestational age, small for gestational age (SGA), large for gestational age (LGA), placenta previa, placental abruption, hypertensive disorders, and gestational diabetes mellitus. RESULT(S): The risk of being born SGA was statistically significantly increased in the EMT ≤7.5 mm group compared with those from the EMT >12 mm group (adjusted odds ratio [aOR] 2.391; 95% confidence interval [CI], 1.155-4.950). Moreover, maternal body mass index, secondary infertility, preterm delivery, and hypertensive disorders were all independent predictors for SGA. The mean birth weights of singletons in women with EMT ≤7.5 mm were lower than in the groups with EMT >7.5-12 mm and EMT >12 mm (3.25 ± 0.56 kg vs. 3.38 ± 0.51 kg and 3.39 ± 0.53 kg, respectively). CONCLUSION(S): After fresh IVF/ICSI-ET, the risk of SGA was increased twofold in women with EMT ≤7.5 mm compared with women with EMT >12 mm. We suggest that women with a thin EMT after obtaining a pregnancy by IVF should receive improved prenatal care to reduce the risk of delivering a SGA infant.

Factors associated with subchorionic hematoma formation in pregnancies achieved via assisted reproductive technologies.

PURPOSE: To determine if certain clinical and/or embryologic factors are independently associated with the increased prevalence of subchorionic hematoma (SCH) among pregnancies achieved via in vitro fertilization (IVF) with fresh embryo transfer (ET). DESIGN: Retrospective chart review. METHODS: In this retrospective study, data were abstracted from 210 autologous oocyte IVF clinical pregnancies that resulted from fresh ET at a single fertility center from January 2012 through December 2016. Clinical and embryology laboratory variables were analyzed as possible factors associated with the presence or absence of SCH in IVF pregnancies via bivariate associations and multivariable logistic regression analyses. Independent variables included prior uterine surgery versus no uterine surgery, peak estradiol, and progesterone levels, day 3 (n = 92) versus day 5 (n = 118) ET, and assisted hatching versus no assisted hatching. Among the day 5 ET subgroup of 118 patients, 117 had data for the variables inner cell mass (ICM) grading and trophectoderm (TE) because one day 5 ET was at the morula stage. RESULTS: We found a significant bivariate association between TE grading and SCH, where cases with TE grade "A" were significantly less likely to have SCH compared with cases with grades "B" or "C." This significant difference remained when adjusting for the other factors considered in a multivariable logistic regression model for the probability of SCH. CONCLUSIONS: The data analyzed here suggest that a less-advanced trophectoderm grade may be a potential factor that is associated with the presence of SCH in pregnancies achieved via IVF.

Effect and Relationship of Seasons on the High Risk of Ovarian Hyperstimulation Syndrome After Oocyte Retrieval in Patients With Polycystic Ovary Syndrome.

Objective: To investigate the effect of seasons on the incidence of high risk of ovarian hyperstimulation syndrome (OHSS) after in oocyte retrieval in patients with polycystic ovarian syndrome (PCOS) and to establish a nomogram to predict the risk of OHSS. Design: Single-center, retrospective study. Setting: University-affiliated reproductive medicine center. Patients: A total of 2,030 infertility patients with PCOS underwent the follicular phase long-acting long protocol IVF/ICSI in the reproductive medicine center from January 2017 to December 2019. Interventions: None. Main outcome measures: Logistic regression analysis was used to analyze the factors associated with a high risk of OHSS. We established a nomogram to predict the risk of OHSS in infertility patients with PCOS after oocyte retrieval. Results: The incidence of patients at high risk of OHSS was significantly different from season-to-season and was especially higher in the summer and winter. Multivariate logistic analysis showed that gonadotropin dosage, number of retrieved oocytes, estradiol level, average bilateral ovarian diameter on the day human chorionic gonadotropin was administered, type of infertility, and average temperature were independent risk factors for OHSS after oocyte retrieval in PCOS patients. Based on the above independent risk factors, we constructed a prediction model for OHSS risk. To evaluate the efficiency of the prediction model, we calculated the C-index (0.849), area under the receiver operating characteristic curve (0.849), and internal validation C-index (0.846). Decision curve analysis suggested that the prediction model exhibited significant net benefits. Conclusions: The incidence of PCOS patients at high risk for OHSS after oocyte retrieval fluctuated with seasonal temperature changes, and was significantly higher in extreme climates. The prediction model had favorable predictive performance and clinical application value.