Safety and Child Health of Assisted Reproduction Technology (ART)

Editors

Yimin Zhu

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University

Yiping Shen

Harvard Medical School

Impact

CON: control group, E2: treat with 10-6M oestrogen, PPT: treat with 10-6M ERα agonist, DPN: treat with 10-6M ERβ agonist, ICI: treat with 10-6M oestrogen receptor antagonist, E2+ICI: treat with both 10-6M E2 and 10-6M ICI. *p<0.05.

Original Research

06 March 2023

Adverse effect of assisted reproductive technology-related hyperoestrogensim on the secretion and absorption of uterine fluid in superovulating mice during the peri-implantation period

Xinru Xia

, 7 more and

Jiayin Liu

2,173 views

4 citations

Original Research

12 August 2022

"Double Frozen Transfer" Could Influence the Perinatal and Children's Growth: A Nested Case-Control Study of 6705 Live Birth Cycles

Jie Gao

, 5 more and

Zi-Jiang Chen

2,188 views

0 citations

Original Research

22 July 2022

An Individualized Recommendation for Controlled Ovary Stimulation Protocol in Women Who Received the GnRH Agonist Long-Acting Protocol or the GnRH Antagonist Protocol: A Retrospective Cohort Study

Ming-Xing Chen

, 12 more and

Yu-Bin Ding

3,157 views

9 citations

ROC, receiver operating characteristic; RIF, recurrent implantation failure, NK, natural killer; Tregs, regulatory T; Tfh, T follicle helper.

Original Research

22 July 2022

Recurrent Implantation Failure May Be Identified by a Combination of Diagnostic Biomarkers: An Analysis of Peripheral Blood Lymphocyte Subsets

Jun-Ying Cai

, 5 more and

Hong Zhou

2,458 views

7 citations

Original Research

14 July 2022

Prognosis of Congenital Anomalies in Conceptions Following In Vitro Fertilization: A Multicenter Retrospective Cohort Study in China

Jie Bao

, 8 more and

Hongbin Chi

4,166 views

3 citations

Original Research

05 July 2022

Risk of Higher Blood Pressure in 3 to 6 Years Old Singleton Born From OHSS Patients Undergone With Fresh IVF/ICSI

Yimin Zhu

, 7 more and

Lanfeng Xing

3,514 views

3 citations

Clinical Trial

29 June 2022

GnRH Antagonist Protocol Versus GnRH Agonist Long Protocol: A Retrospective Cohort Study on Clinical Outcomes and Maternal-Neonatal Safety

Jieru Zhu

, 3 more and

Jianping Ou

Objective: To evaluate the clinical outcomes and maternal-neonatal safety of gonadotropin releasing hormone antagonist (GnRH-ant) and gonadotropin releasing hormone agonist (GnRH-a) protocols.

Methods: A total of 2505 women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were retrospectively analyzed. Patients were divided into GnRH-ant group (n = 1514) and GnRH-a group (n = 991) according their stimulation protocol. Propensity Score Matching (PSM) was used for balancing the baseline of two groups. The pregnancy outcomes were analyzed in fresh transfer cycles, and the obstetric and perinatal outcomes were calculated in singleton live births of fresh cycles. The primary outcome was the live birth rate. The secondary outcome measures were maternal complications, preterm birth rate, low birthweight rate, multiple pregnancy rate, and moderate-severe OHSS rate.

Results: After 1:1 PSM, baseline characteristics of the GnRH-ant group and GnRH-a group were matched and assigned 991 cycles in each group. Before PSM, there were 700 fresh cycles including 237 singleton live births in the GnRH-ant group and 588 fresh cycles including 187 singleton live births in the GnRH-a group. After PSM, there were 471 fresh cycles including 166 singleton live births in the GnRH-ant group and 588 fresh cycles including 187 singleton live births in the GnRH-a group. No significant differences were observed in the live birth rate (44.6% vs 48.8%), maternal complications, preterm birth rate (9.0% vs 6.4%), and low birthweight rate (17.5% vs 24.1%) between two groups after PSM (P > 0.05). The moderate-severe OHSS rate (2.9% vs 6.0%, P = 0.002) and multiple pregnancy rate (24.5% vs 33.1%, P = 0.025) was significantly lower in the GnRH-ant group than that in the GnRH-a group after PSM.

Conclusion: GnRH-ant protocol was comparable with GnRH-a protocol in clinical outcomes, obstetric and perinatal outcomes, and with a lower risk of OHSS. For those who want to get an effective and safe outcome, and a shorter treatment period, GnRH-ant is a suitable choice.

4,278 views

16 citations

Original Research

27 June 2022

Early Spontaneous Abortion in Fresh- and Frozen-Embryo Transfers: An Analysis of Over 35,000 Transfer Cycles

Jun Shuai

, 4 more and

Hong Ye

3,740 views

4 citations

Original Research

24 June 2022

Fetal Reduction Could Improve but Not Completely Reverse the Pregnancy Outcomes of Multiple Pregnancies: Experience From a Single Center

Zhu Yimin

, 6 more and

Xing Lanfeng

Objective: To investigate the effectiveness and limitations of multifetal pregnancy reduction (MFPR) on the improvement of pregnancy outcomes of triplet or twin pregnancies conceived by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Methods: We performed a cohort study of women undergoing IVF or ICSI from 2002–2016 in reproductive center, women’s hospital, Zhejiang University School of Medicine. The cohort included 502 women who underwent MFPR and 9641 non-reduced women. Pregnancy outcomes were gestational age (GA) at delivery, pregnancy loss, preterm delivery, low birth weight (LBW), very low birth weight (VLBW), and small for gestational age (SGA). Multiple linear regression and logistic regression models were used to compare pregnancy outcomes between groups.

Results: Triplets reduced to singletons had a longer median GA (39.07 vs 37.00, P<0.001), and lower rates of LBW (8.9% vs 53.2%, P<0.001) and SGA (17.8% vs 44.7%, P=0.001) than triplets reduced to twins, with a similar pregnancy loss rate (6.7% vs 6.6%, P=0.701). Twins reduced to singletons had a comparable pregnancy loss rate (4.8% vs. 6.5%, P=0.40), a longer median GA (38.79 vs. 37.00, P<0.001), and lower rates of LBW (13.5% vs. 47.0%, P<0.001) and SGA (13.5% vs. 39.6%, P<0.001) than primary twins. Triplets reduced to twins had higher rates of LBW (53.2% vs. 47.0%, P=0.028) and SGA (44.7% vs. 39.6%, P=0.040) than primary twins, with a similar pregnancy loss rate (6.6% vs. 6.5%, P=0.877). Singletons reduced from triplets/twins had higher rates of preterm delivery (15.8% vs. 7.3%, P<0.001), LBW (12.3% vs. 4.32%, P<0.001), VLBW (2.3% vs. 0.4%, P=0.002), and SGA (14.6% vs.6.6%, P<0.001) than primary singletons, with a comparable pregnancy loss rate (5.3% vs. 5.4%, P=0.671).

Conclusions: This study suggests that the pregnancy loss rate is similar between reduction and non-reduction groups. MFPR improves pregnancy outcomes, including the risk of preterm delivery, LBW, and SGA, but still could not completely reverse the adverse pregnancy outcomes of multiple pregnancies.

3,814 views

12 citations

Original Research

23 June 2022

Which Factors Are Associated With Reproductive Outcomes of DOR Patients in ART Cycles: An Eight-Year Retrospective Study

Lu Li

, 3 more and

Yingpu Sun

2,459 views

5 citations

Original Research

21 June 2022

Effects of Anticoagulants and Immune Agents on Pregnancy Outcomes and Offspring Safety in Frozen-Thawed Embryo Transfer Cycles—A Retrospective Cohort Study

Yanli Fan

, 6 more and

Guimin Hao

5,193 views

0 citations

Original Research

15 June 2022

Intracytoplasmic Sperm Injection May Not Improve Clinical Outcomes Despite Its Positive Effect on Embryo Results: A Retrospective Analysis of 1130 Half-ICSI Treatments

Nan Peng

, 6 more and

Mei Li

2,431 views

7 citations

Original Research

15 June 2022

Predictive Factors for Recovery Time in Conceived Women Suffering From Moderate to Severe Ovarian Hyperstimulation Syndrome

Kai Huang

, 3 more and

Jun Zhai

4,775 views

4 citations

Original Research

06 June 2022

Adverse Effects of Polycystic Ovarian Syndrome on Pregnancy Outcomes in Women With Frozen-Thawed Embryo Transfer: Propensity Score-Matched Study

Zhexin Ni

, 6 more and

Chaoqin Yu

Purpose: This work aimed to evaluate the adverse effect of polycystic ovary syndrome (PCOS) on pregnancy outcomes of singletons after vitrification in women with frozen-thawed embryo transfer (FET).

Methods: Patients with/without PCOS who underwent FET from January 2013 and December 2018 were included. Propensity score matching (PSM) was used to reduce the influence of bias. Logistic regression was applied to identify the risk factors of adverse pregnancy outcomes of singletons in women with PCOS.

Result: After PSM, the PCOS group had shorter gestational age (P<0.001) and lower newborn birth weight than the non-PCOS group (P=0.045). Compared with the non-PCOS group, the PCOS group had an increased risk of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) (P<0.001), placenta and membrane abnormality (P<0.001), stillbirth (P<0.001), neonatal complication (P=0.014), and miscarriage rate (P<0.001). Neonatal complication was associated with parity (adjusted OR=1.202, 95% CI=1.002–1.443, P=0.048) and basal P level (adjusted OR=1.211, 95% CI=1.021–1.436, P=0.028). According to multivariable logistic regression analysis, the miscarriage rate was related to parity (adjusted OR=1.201, 95% CI=1.057–1.166, P=0.005) and basal E2 (adjusted OR=1.002, 95% CI=1.000–1.004, P=0.019) and P levels on the day of embryo transfer (adjusted OR=0.971, 95% CI=0.957–0.985, P<0.001).

Conclusions: Compared with non-PCOS women, women with PCOS have a higher risk of GDM and PIH, and neonatal complications and therefore require additional care during pregnancy and parturition.

4,182 views

12 citations

Original Research

10 June 2022

Follicular-Phase GnRH Agonist Protocol Is Another Choice for Polycystic Ovary Syndrome Patients With Lower LH/FSH and Lower AMH Levels Without Increasing Severe OHSS Risk

Rui Gao

, 4 more and

Peng Bai

3,180 views

2 citations

Original Research

03 June 2022

Association of Polycystic Ovary Syndrome Phenotypes With Adverse Pregnancy Outcomes After In-Vitro Fertilization/Intracytoplasmic Sperm Injection

Qiumin Wang

, 5 more and

Yuhua Shi

Objective: This study aims to evaluate the association between polycystic ovary syndrome (PCOS) phenotypes and adverse perinatal outcomes, comparing the characteristics, ovarian response, and assisted reproductive outcomes in patients with various PCOS phenotypes after in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Methods: This study comprised 6,732 patients who underwent the first cycle of IVF/ICSI treatment in our outpatient department from January 2017 to July 2018. Propensity score matching (PSM) was used in PCOS and non-PCOS groups to balance the influence of intergroup confounding factors. After the PSM procedure, 1,186 patients were included in the two groups, and the PCOS patients were further divided into four PCOS phenotype groups based on the Rotterdam criteria.

Results: Patients with various PCOS phenotypes had similar rates of biochemical pregnancy, clinical pregnancy, and live birth (all P-values > 0.05). The overall incidence of adverse pregnancy outcomes (including ectopic pregnancy, miscarriage, preterm birth) was significantly higher in PCOS phenotype A and D groups than in the control group (44% and 46.4% vs. 28.7%, P = 0.027). The rates of hypertensive disorder of pregnancy (HDP) were significantly higher in PCOS phenotype A and C groups than in the control group (9.3% and 12.5% vs. 3.1%, P = 0.037). After adjustment for potential confounders, the differences in adverse pregnancy outcomes persisted (P = 0.025).

Conclusions: The overall incidence of adverse pregnancy outcomes is higher in women with PCOS phenotypes A and D than in women with non-PCOS.

4,639 views

13 citations

Original Research

23 May 2022

Pregnancy and Perinatal Outcomes of Patients With Prior Cesarean Section After a Single Embryo Transfer in IVF/ICSI: A Retrospective Cohort Study

Lin Wang

, 3 more and

Feiyang Diao

SET, single embryo transfer; VD, vaginal delivery; CD, cesarean delivery; PSM, propensity score matching; CSD, cesarean scar defect.

Objective: To study the influence of the previous cesarean section on the pregnancy outcomes and perinatal outcomes in single embryo transfer (SET) cycles in an in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) setting compared to those with previous vaginal delivery (VD). In addition, the association between fertility outcomes and different cesarean scar defect (CSD) sizes was studied.

Method: This was a retrospective cohort study conducted in the Reproductive Center of the First Affiliated Hospital of Nanjing Medical University. A total of 4,879 patients with previous delivery history undergoing SET were included between January 2015 and April 2019. Patients were divided into the VD group and cesarean delivery (CD) group according to different modes of previous delivery. The primary outcome was live birth rate. The pregnancy outcomes of CD were analyzed as a subgroup and the relationship between pregnancy outcomes as well as the different sizes of CSD were explored by logistic regression analysis.

Results: There were no significant differences in live birth rate, clinical pregnancy rate, and miscarriage rate between the CD group and VD group. The incidence rates of pregnancy complications such as pregnancy hypertension, gestational diabetes mellitus, placenta abnormalities, premature rupture of membrane, and postpartum hemorrhage were similar in the two groups. Live birth rate was significantly lower in the CSD group (23.77% vs 37.01%, aOR: 0.609, 95% CI: 0.476-0.778) comparing to patients without CSD. There were also significant differences in clinical pregnancy rate (37.52% vs 47.64%, aOR: 0.779, 95%CI: 0.623-0.973) and miscarriage rate (34.55% vs 20.59%, aOR: 1.407, 95%CI:1.03-1.923). Large size CSD significantly decreased live birth rate (13.33% vs 26.29%, aOR: 0.422, 95%CI: 0.197-0.902) and clinical pregnancy rate (25.33% vs 40.09%, aOR: 0.503, 95%CI: 0.272-0.930) compared with small size CSD.

Conclusion: For women with previous cesarean sections, the pregnancy outcomes were similar to those with previous VD without increased perinatal complications following SET. The presence of CSD was associated with a marked reduction in live birth rate, especially in patients with large size CSD.

3,175 views

21 citations

Original Research

24 May 2022

Birthweight After Frozen Embryos Formed on the Fifth Day Versus the Sixth Day: A Retrospective Analysis Including 17,127 Singleton Newborns

Junlan Yang

, 5 more and

Rong Tang

1,981 views

4 citations

Original Research

14 April 2022

Insulin Resistance is a Risk Factor for Early Miscarriage and Macrosomia in Patients With Polycystic Ovary Syndrome From the First Embryo Transfer Cycle: A Retrospective Cohort Study

Yuanhui Chen

, 2 more and

Cuilian Zhang

Objective: The objective of the study was to explore the effect of insulin resistance on pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) from the first embryo transfer cycle.

Design: This was a single-center, retrospective, observational cohort study.

Patients: Included in the study were women with PCOS for the first embryo transfer.

Main Outcome Measures: Early miscarriage rate and macrosomia rate were the main outcome measures.

Results: With increased HOMA-IR, the early miscarriage rate (7.14, 13.21, and 16.22%, respectively; P = 0.039), macrosomia rate (5.78, 11.79, and 17.58%, respectively; P = 0.026) and the incidence of gestational diabetes (GDM) (10.00, 14.50, and 25.67% respectively; P = 0.002) significantly increased, while the live birth rate markedly decreased (63.03, 55.27, and 47.88%, respectively; P = 0.004). No significant difference was found in clinical pregnancy rate, late miscarriage rate, low birthweight rate and baby gender ratio (all P >0.05). After adjusting for confounding factors, HOMA-IR was an independent risk factor of early miscarriage rate and macrosomia rate.

Conclusion: Insulin resistance is an independent risk factor for early miscarriage and macrosomia in PCOS patients during the first embryo transfer cycle. It is essential to give more attention before and after pregnancy for PCOS women with high HOMA-IR.

4,214 views

20 citations