The influence of uterine fibroids on adverse outcomes in pregnant women: a meta-analysis.

OBJECTIVE: The objective of the meta-analysis was to determine the influence of uterine fibroids on adverse outcomes, with specific emphasis on multiple or large (≥ 5 cm in diameter) fibroids. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and SinoMed databases for eligible studies that investigated the influence of uterine fibroids on adverse outcomes in pregnancy. The pooled risk ratio (RR) of the variables was estimated with fixed effect or random effect models. RESULTS: Twenty-four studies with 237 509 participants were included. The pooled results showed that fibroids elevated the risk of adverse outcomes, including preterm birth, cesarean delivery, placenta previa, miscarriage, preterm premature rupture of membranes (PPROM), placental abruption, postpartum hemorrhage (PPH), fetal distress, malposition, intrauterine fetal death, low birth weight, breech presentation, and preeclampsia. However, after adjusting for the potential factors, negative effects were only seen for preterm birth, cesarean delivery, placenta previa, placental abruption, PPH, intrauterine fetal death, breech presentation, and preeclampsia. Subgroup analysis showed an association between larger fibroids and significantly elevated risks of breech presentation, PPH, and placenta previa in comparison with small fibroids. Multiple fibroids did not increase the risk of breech presentation, placental abruption, cesarean delivery, PPH, placenta previa, PPROM, preterm birth, and intrauterine growth restriction. Meta-regression analyses indicated that maternal age only affected the relationship between uterine fibroids and preterm birth, and BMI influenced the relationship between uterine fibroids and intrauterine fetal death. Other potential confounding factors had no impact on malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH. CONCLUSION: The presence of uterine fibroids poses increased risks of adverse pregnancy and obstetric outcomes. Fibroid size influenced the risk of breech presentation, PPH, and placenta previa, while fibroid numbers had no impact on the risk of these outcomes.

Prediction of embryo euploidy and pregnancy outcome by blastocyst morphology and development speed for women receiving single embryo transfer.

BACKGROUND: Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. METHODS: A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. RESULTS: The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P < 0.001), and the euploid rate of morphologically high-grade blastocysts was significantly greater than that of non-high-grade blastocysts. Development speed D5 (OR = 1.6, 95% CI 1.2-2.2, P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5-2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. CONCLUSION: The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade.

Assisted reproductive technology physicians are actively exploring methods to improve the accuracy of embryo selection for successful pregnancy. We evaluated the associations of embryo morphological grade and development speed with chromosomal status and clinical outcome for couples without a history of infertility, in vitro fertilisation failure, or recurrent miscarriage receiving euploid embryo transfer. Blastocysts from females younger than 35 years, of high morphological grade, and demonstrating faster development speed were most likely to be euploid (least likely to have chromosomal abnormalities). Alternatively, patients implanted with slower developing euploid blastocysts were at higher risk of early pregnancy loss. To maximise the probability of implanting euploid embryos and minimise the risk of pregnancy loss, the selection order of embryo transferred should be based on embryo development speed followed by morphological grades.

Comparison of pregnancy outcomes among patients of different ages who underwent frozen-thawed high-quality single blastocyst transfer.

OBJECTIVE: To investigate the feasibility of performing frozen-thawed high-quality single blastocyst transfer in women of different ages. METHODS: A total of 1,279 women were divided into four groups: a 38-40-year-old group (n = 147), 35-37-year-old group (n = 164), 30-34-year-old group (n = 483), and < 30-year-old group (n = 485). Intergroup comparisons of baseline characteristics and pregnancy and neonatal outcomes were made. RESULTS: The clinical pregnancy rate (47.6%), and live birth rate (34.0%) in the 38-40-year-old group were significantly lower than those in the 30-34-year-old group (64.4%, 50.9%, respectively; all P < 0.001) and < 30-year-old group (62.9%, 50.7%, respectively; all P < 0.001). However, the 35-37-year-old group did not differ from the other three groups in these two dimensions (all P > 0.05). Moreover, there were no differences in the rates of biochemical pregnancy, miscarriage, or obstetric or neonatal complications among the four groups (all P > 0.05). According to the multivariate logistic regression analysis, the 35-37-year-old group was not associated with non-live birth outcomes, adverse pregnancy outcomes, or obstetric or neonatal complications. However, being 38-40 years of age was a risk factor for non-live birth (OR = 2.121, 95% CI: 1.233-3.647) and adverse pregnancy outcomes (OR = 1.630, 95% CI: 1.010-2.633). Post hoc power analysis showed that the study was sufficiently powered to detect meaningful differences. CONCLUSION: Frozen-thawed high-quality single blastocyst transfer produces the same satisfactory pregnancy outcomes for women aged 35-37 years as younger patients. Future prospective randomized controlled studies with larger populations are needed to verify the feasibility and safety of this method.

Early intrauterine pregnancy with an intrauterine device in place and terminated with spontaneous abortion: A case report.

RATIONALE: The overall pregnancy rate in individuals with an intrauterine device (IUD) for contraception is <1%. If pregnancy occurs while an IUD is in place, there is a higher risk of an ectopic pregnancy. We report the case of a woman with an IUD who was 7 weeks pregnant and experienced a spontaneous abortion 1 week later. PATIENT CONCERN: A 32-year-old woman presented to our outpatient department with intermittent vaginal staining for several days. DIAGNOSES: She was 7 weeks pregnant and had an IUD in place for over 4 years. A vaginal examination revealed no vaginal bleeding and no blood clots; however, a parous cervix was observed. The IUD string was not visible. Transvaginal ultrasonography revealed a gestational sac in the uterine cavity, with a fetal pole and a crown-rump length of 11.4 mm. The fetal heart rate was 159 beats/min. The IUD was located in the retroplacental region. The bilateral adnexa appeared normal (right ovary, 2.9 cm; left ovary, 2.5 cm). The patient was diagnosed with an intrauterine pregnancy with an IUD in place and threatened abortion. INTERVENTIONS: Attempts to remove the IUD were abandoned due to its location, and conservative treatment was initiated with Utrogestan (100 mg) administered 3 times a day for 1 week. Bed rest was advised. OUTCOMES: Unfortunately, she experienced a complete abortion 1 week later. LESSONS: The novelty of this case report lies in the rare occurrence of an intrauterine pregnancy with a long-term IUD in place, the challenges posed by the IUD's specific location, and the complex management of threatened abortion in this context. Our case highlights the diagnostic management approach for intrauterine pregnancy with an IUD in place. Furthermore, it explores the impact of IUD location on pregnancy prognosis.

Lack of association between COVID-19 vaccines and miscarriage onset using a case-crossover design.

Pregnant women might have an increased risk of SARS-COV-2 infection. Although evidence towards the efficacy and safety of COVID-19 is growing still there is room for improvement on the knowledge towards pregnancy adverse events, such as miscarriage. We explored the association of COVID-19 vaccine with the risk of miscarriages using the Real-World. We identified a cohort of vaccinated pregnancies using the BIFAP database which contains systematically recorded data on care patients in Spain (N = 4054). We then restricted it to those women who had a miscarriage using a validated algorithm (N = 607). Among them, we performed a case-crossover design to evaluate the effect of intermittent exposures on the risk of miscarriage. Adjusted Odds Ratio with their confidence intervals were calculated using two analytical approaches: conditional logistic regression and Generalized Linear Mixed-Effects Models. A total of 225 (37.1%) were aged 35-39 years. The most common comorbidities were asthma, migraine, gastritis, and hypothyroidism. A total of 14.7% received only one dose of COVID-19 and 85.3% two doses, respectively. A total of 36.8% of women with one dose and 27.6% with two doses received the vaccine 7 days prior to the miscarriage. Corresponding adjusted estimates for the risk of miscarriage using the conditional logistic regression where as follows: 1.65 (95% CI 0.85-3.23) when using as the sum of 3 control moments among women with one dose, 1.02 (95% CI 0.72-1.46) among women with two doses and 1.03 (95% CI 0.72, 1.46) using the whole study population. Very similar results were obtained when conducting the Generalized Linear Mixed-Effects Models. There was no overall increased risk of miscarriage onset associated with COVID-19 vaccine although contradictory results were found according to the number of doses. Further studies are required with larger sample sizes to assess this association.

The effect of ß-cell dysfunction on reproductive outcomes of PCOS undergoing IVF or ICSI embryo transfer cycles: a retrospective cohort study.

Objective: To investigate the effects of ß-cell dysfunction on IVF outcomes in women with PCOS. Methods: This retrospective cohort study includes 1,212 women with PCOS undergoing their first IVF cycle between September 2010 and December 2019. Beta-cell dysfunction was measured by homeostasis model assessment of ß-cell function (HOMA-ß) index. Results: In quartiles of HOMA-ß, the incidence of miscarriage dramatically increased from 10.2% (Q1) to 31.1% (Q4) (P for trend <0.001). Likewise, the incidence of miscarriage in quartiles of HOMA-ß also showed a similar trend (P for trend <0.001). After adjusting for confounding factors, logistic regression analyses showed that high HOMA-IR values were independently associated with a high risk of miscarriage, with the odds ratios (OR) and 95% confidence intervals for quartiles 2-4 versus quartile 1 were 1.30 (0.69-2.46), 1.82 (0.97-3.43), and 3.57 (1.86-6.85), respectively (P for trend <0.001). When analyzed jointly, women in the highest HOMA-IR and highest HOMA-ß group exhibited the highest risk for miscarriage compared with all other groups. Furthermore, higher HOMA-IR values were associated with higher risks of miscarriage among PCOS women regardless of HOMA-ß values. Conclusions: ß-cell dysfunction is independently associated with increased miscarriage rate and decreased live birth rate in women with PCOS. It also plays a synergistic role with IR in terms of the reproductive outcomes, while the influence of IR overweighs that of ß-cell dysfunction.

The impact of first-trimester subchorionic hematomas on pregnancy outcomes after euploid embryo transfer: a retrospective cohort study.

BACKGROUND: The aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer. METHODS: We retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors. RESULTS: A total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio [aOR] 1.99, 95% confidence interval [CI] 1.25-3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39-0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups. CONCLUSIONS: The presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.

Female obesity increases the risk of preterm birth of single frozen-thawed euploid embryos: a retrospective cohort study.

INTRODUCTION: Obesity has been associated with an increased risk of reproductive failure, especially preterm birth. As preimplantation genetic testing for aneuploidies (PGT-A) is increasingly used worldwide, however, it is still unclear whether body mass index (BMI) has an effect on the preterm birth rate in patients undergoing in vitro fertilization (IVF) with PGT-A when transferring a single euploid blastocyst. MATERIALS AND METHODS: This retrospective, single-center cohort study included 851 women who underwent the first cycle of frozen-thawed single euploid blastocyst transfer with PGT-A between 2015 and 2020. The primary outcome was the preterm birth rate. Secondary outcomes were clinical pregnancy, miscarriage, ectopic pregnancy, pregnancy complications, and live birth. RESULTS: Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n = 81), normal weight (18.5-24.9, n = 637), overweight (25-30, n = 108), and obese (≥30, n = 25). There was no difference in the clinical pregnancy, miscarriage, ectopic pregnancy, pregnancy complication, and live birth by BMI category. In multivariate logistic regression analysis, preterm birth rates were significantly higher in women with overweight (adjusted odds ratio [aOR] 3.18; 95% confidence interval [CI], 1.29-7.80, p = .012) and obese (aOR 1.49; 95% CI, 1.03-12.78, p = .027) compared with the normal weight reference group. CONCLUSION: Women with obesity experience a higher rate of preterm birth after euploid embryo transfer than women with a normal weight, suggesting that the negative impact of obesity on IVF and clinical outcomes may be related to other mechanisms than aneuploidy.

An Estrogen-NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage.

Endometriosis is a common estrogen-dependent condition that impacts 8-10% of women in their reproductive age, resulting in notable pain, morbidity, and infertility. Despite extensive research endeavors, the precise cause of endometriosis remains elusive, and the mechanisms contributing to its associated infertility are still not well comprehended. Natural killer (NK) cells, vital innate immune cells crucial for successful pregnancy, have been investigated for their potential involvement in the pathogenesis of endometriosis. Prior research has mainly concentrated on the diminished cytotoxicity of NK cells in endometrial fragments that evade the uterus. Interestingly, accumulating evidence suggests that NK cells play multifaceted roles in regulating the biology of endometrial stromal cells (ESCs), promoting local immune tolerance, influencing endometrial receptivity, oocyte development, and embryo implantation, thereby contributing to infertility and miscarriage in patients with endometriosis. In this comprehensive review, our goal is to summarize the current literature and provide an overview of the implications of NK cells in endometriosis, especially concerning infertility and pregnancy loss, under the influence of estrogen.

[Intrauterin infection during the first trimester and on-going pregnancy]. / Cas clinique. Infection intra-utérine au premier trimestre d'une grossesse évolutive.

An intrauterine infection during the first trimester of pregnancy can rapidly lead to bacteremia, with severe consequences for the patient. While these infections are mainly found after a miscarriage or an abortion, the diagnosis is sometimes made while the pregnancy is still in progress. The clinical history and symptoms reported by the patient lead to the suspicion of such a complication. Treatment must be rapid and based on a broad-spectrum antibiotic regimen covering Gram-negative, Gram-positive, aerobic and anaerobic bacteria. As soon as the treatment has been initiated, uterine curettage should be performed to remove the infected material, whether or not foetal cardiac activity is present at the time of diagnosis.

Une infection intra-utérine durant le premier trimestre de la grossesse peut rapidement mener à une bactériémie et avoir des conséquences sévères pour la patiente. Alors que ces infections sont principalement retrouvées après une fausse couche ou une interruption volontaire de grossesse, le diagnostic est parfois posé alors que la grossesse est évolutive. L'histoire clinique et les symptômes rapportés par la patiente permettent de suspecter une telle complication. La prise en charge doit être rapide et repose sur un traitement antibiotique à large spectre couvrant les bactéries Gram négatif, Gram positif, les aérobies et les anaérobies. Dès le traitement instauré, un curetage utérin devra être réalisé afin d'éliminer le matériel infecté, que l'activité cardiaque fœtale soit présente ou non au moment du diagnostic.

Association with pre-pregnancy BMI on early pregnancy loss in infertility patients in first HRT-FET cycles: A retrospective cohort study.

OBJECTIVE: To investigate the association between pre-pregnancy body mass index (BMI) and the early pregnancy loss rate in patients in first hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) cycles and find the threshold. METHODS: A retrospective cohort study was conducted using a total of 14030 HRT-FET cycles at the Reproductive Center from January 2017 to December 2021. The association of pre-pregnancy BMI on early pregnancy loss rate in patients in HRT-FET cycles was assessed by performing univariate analysis, multivariable logistic regression, curve fitting and threshold effect analysis. RESULTS: There were 2076 cycles of early pregnancy loss, and the pregnancy loss rate was 14.80%. After adjusting for confounding factors, the early pregnancy loss rate of the obese group was significantly higher than that of the normal weight group (P < 0.05). The threshold effect analysis showed that as the pre-pregnancy BMI ranged from 21.2 to 25.8 kg/m2, the early pregnancy loss rate came to the plateau phase at the low level. In addition, when the BMI was ≥ 25.8 kg/m2, the early pregnancy loss rate increased by 3% (aOR = 1.03, P = 0.01) with each 1 kg/m2 increment of BMI. CONCLUSION: The early pregnancy loss rate might achieve a low level when the pre-pregnancy BMI was within the range of 21.2- 25.8 kg/m2. The early pregnancy loss rate would increase when pre-pregnancy BMI is more than 25.8 kg/m2. For patients in HRT-FET cycles, adjusting their pre-pregnancy BMI to the optimal level by following a healthy diet and daily exercise may help to reduce the early pregnancy loss.

Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.

Pregnancy Outcomes After Laparoscopic Radiofrequency Ablation of Uterine Leiomyomas Compared With Myomectomy.

OBJECTIVE: To compare pregnancy outcomes after laparoscopic radiofrequency ablation and myomectomy. METHODS: The ULTRA (Uterine Leiomyoma Treatment With Radiofrequency Ablation) study is an ongoing multicenter prospective cohort study with longitudinal follow-up up to 5 years comparing outcomes of radiofrequency ablation with myomectomy in premenopausal women older than age 21 years with symptomatic uterine leiomyomas. Participants were queried every 6 months after surgery to assess the incidence of pregnancy and pregnancy outcomes. RESULTS: Among 539 women enrolled in ULTRA, a total of 37 participants (mean age at first pregnancy 35.0±4.7 years) conceived 43 times as of March 2023 (22 radiofrequency ablation, 21 myomectomy). The average length of follow-up time after all procedures was 2.5±1.0 years. The baseline miscarriage rate in the study population was 33.3%. In participants who underwent radiofrequency ablation, 9 of 22 pregnancies (40.9%, 95% CI, 20.3-61.5%) ended in first-trimester miscarriage, 11 resulted in live births (50.0%, 95% CI, 29.1-70.9%), one resulted fetal death at 30 weeks of gestation, and one resulted in uterine rupture during miscarriage treatment with misoprostol 10 weeks after radiofrequency ablation. Among the live births in the radiofrequency ablation group, 45.5% were by vaginal delivery. In the myomectomy group, 9 of 21 pregnancies (42.9%, 95% CI, 21.7-64.0%) ended in first-trimester miscarriage and 12 resulted in live births (57.1%, 95% CI, 36.0-78.3%). There were no significant differences in the likelihood of live birth or miscarriage between the study groups. CONCLUSION: Full-term pregnancy and vaginal delivery are achievable after radiofrequency ablation of leiomyomas. However, in this interim analysis, the miscarriage rate in both radiofrequency ablation and myomectomy groups was higher than expected for women in this age group. Long-term data collection in the ongoing ULTRA study aims to further understand pregnancy outcomes after radiofrequency ablation compared with myomectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT0210094.

High Incidence of CPLANE1-Related Joubert Syndrome in the Products of Conceptions from Early Pregnancy Losses

Background: The fetal monogenic causes of early pregnancy losses (EPLs) are mainly unknown, with only a few articles on the subject published. In our previous study of EPLs using whole-exome sequencing analysis, we confirmed a genetic diagnosis of CPLANE1-related Joubert syndrome (JS) in three EPLs from two couples and identified a relatively common CPLANE1 allele among our population (NM_001384732.1:c.1819delT;c.7817T>A, further after referred as "complex allele"). Pathogenic variants in the CPLANE1 (C5orf42) gene are reported to cause JS type 17, a primary ciliopathy with various system defects. Aims: To examine the hypothesis that the CPLANE1 "complex allele," whether homozygous or compound heterozygous, is a common cause of EPLs in our population. Study Design: Cohort study/case-control study.ontrol study. Methods: In this study, we used polymerase chain reaction-based methods to screen for CPLANE1 "complex allele" presence among 246 euploid EPLs (< 12 gestational weeks) from families in North Macedonia. We also investigated the impact of this allele in 650 women with EPLs versus 646 women with no history of pregnancy loss and at least one livebirth, matched by ethnic origin. Results: We found a high incidence of JS in the total study group of EPLs (2.03%), with a considerably higher incidence among Albanian families (6.25%). Although not statistically significant, women with EPLs had a higher allele frequency of the CPLANE1 "complex allele" (AF = 1.38%) than the controls (AF = 0.85%; p = 0.2). Albanian women had significantly higher frequency of the "complex allele" than the Macedonians (AF = 1.65% and 0.39%, respectively; p = 0.003). Conclusion: To the best of our knowledge, this is the highest reported incidence of fetal monogenic disease that might cause EPLs. Targeted screening for the CPLANE1 "complex allele" would be warranted in Albanian ethnic couples because it would detect one JS in every 16 euploid EPLs. Our findings have a larger impact on the pathogenesis of pregnancy loss and contribute to a better understanding of the pathogenicity of the variants in the CPLANE1 gene.

Intrauterine adhesion in ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA): a randomised controlled trial.

BACKGROUND: Intrauterine adhesion (IUA) can arise as a potential complication following uterine surgery, as the surgical procedure may damage the endometrial stratum basalis. The objective of this study was to assess and compare the occurrence of IUA in women who underwent ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA) for managing first-trimester miscarriage. METHODS: This was a prospective, single-centre, randomised controlled trial conducted at a university-affiliated tertiary hospital. Chinese women aged 18 years and above who had a delayed or incomplete miscarriage of ≤ 12 weeks of gestation were recruited in the Department of Obstetrics and Gynaecology at the Prince of Wales. Recruited participants received either USG-MVA or EVA for the management of their miscarriage and were invited for a hysteroscopic assessment to evaluate the incidence of IUA between 6 and 20 weeks after the surgery. Patients were contacted by phone at 6 months to assess their menstrual and reproductive outcomes. RESULTS: 303 patients underwent USG-MVA or EVA, of whom 152 were randomised to 'USG-MVA' and 151 patients to the 'EVA' group. Out of the USG-MVA group, 126 patients returned and completed the hysteroscopic assessment, while in the EVA group, 125 patients did the same. The incidence of intrauterine adhesion (IUA) was 19.0% (24/126) in the USG-MVA group and 32.0% (40/125) in the EVA group, showing a significant difference (p < 0.02) between the two groups. No significant difference in the menstrual outcomes at 6 months postoperatively between the two groups but more patients had miscarriages in the EVA group with IUA. CONCLUSIONS: IUAs are a possible complication of USG-MVA. However, USG-MVA is associated with a lower incidence of IUA postoperatively at 6-20 weeks. USG-MVA is a feasible, effective, and safe alternative surgical treatment with less IUA for the management of first-trimester miscarriage. TRIAL REGISTRATION: The study was registered with the Centre for Clinical Research and Biostatics- Clinical Trials Registry (CCRBCTR), which is a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) (Unique Trial Number: ChiCTR1900023198 with the first trial registration date on 16/05/2019).

Raised First Trimester Thyroid Peroxidase Antibodies May Predict First Trimester Miscarriage: A Case Control Study.

Miscarriages constitute a significant aspect of failed pregnancies and a source of worry for the patient and caregiver. Some of the causes of miscarriages remain unknown. Immunological conditions such as thyroid autoimmunity could play significant roles. Our objective was to determine the relationship between raised thyroid peroxidase antibodies and first trimester miscarriages in a low resource setting. This was a case control study at the Gynaecological Clinic of the University of Calabar Teaching Hospital, Nigeria; from 14th February 2020 to 13th January 2021, involving 145 cases who had first trimester miscarriages, and their matched controls who had apparently normal pregnancies, at same gestational ages. Sera of venous blood from both participants and controls were analysed for thyroid peroxidase antibodies using enzyme-linked immunosorbent assay, and analysed using SPSS version 20, and GraphPad Prism 8.4.3 statistical software. Being a civil servant and low social status had significant odds for first trimester miscarriage. Raised thyroid peroxidase antibodies in the first trimester had 10-fold odds for miscarriage. Odds ratio 10.34, 95% CI: 3.22 to 32.98, P-value = 0.0001. The test had a sensitivity of 89.66% and specificity of 54.41%. The positive predictive value was 17.93%, while the negative predictive value was 97.93% and a likelihood ratio of 1.966. Rising thyroid peroxidase antibodies in early pregnancy could be a predictor for miscarriage. This is so because patients with raised thyroid peroxidase antibodies in the first trimester had a 10-fold risk of having a first trimester miscarriage.

A randomized, controlled clinical study of low-molecular-weight heparin improving pregnancy outcomes in PCOS women undergoing IVF: study protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS), an incidence of 10-15% in women of reproductive age, shows sex hormone disorders, luteal insufficiency, and the tendency of placental villus space thrombus. The incidence of early pregnancy loss in women with PCOS is three to eight times higher than that in non-PCOS women. PCOS women were reported in a pre-thrombotic state, which was manifested by accelerated thrombin production, increased PAI-1 activity, and fibrinogen. Other research also found an over-activated state of women with PCOS in immune system. Therefore, changing the prethrombotic state of PCOS through anticoagulation may be a new way to improve the adverse pregnancy outcome of PCOS. Low-molecular-weight heparin (LMWH) is the most common used anticoagulant drug in pregnancy, and it also was proposed for the prevention of recurrent abortion, although the application of LMWH in PCOS population during early pregnancy has not been reported. The objective of this study is to investigate the effect of LMWH on pregnancy outcomes after invitro fertilization-frozen embryo transfer (IVF-FET) in patients with polycystic ovary syndrome. METHODS: A total of 356 PCOS women aged between 20 and 38 years which prepared for IVF followed with FET will be enrolled in the study. The patients, from four different hospitals stratified by age and body mass index (BMI), will be randomly divided into the study group who will be treated with LMWH started on the day of progesterone transformation (hormone therapy) during FET cycle and the control group without additional medicine. Serum or urine hCG test will be given 14 days after embryo transfer to confirm biochemical pregnancy. If pregnancy is positive, LMWH+ hormone therapy/hormone therapy will be continued for another 2 weeks. Transvaginal ultrasonography will be performed 14 days later to confirm intrauterine pregnancy. The primary outcome is the ongoing pregnancy, which is defined as intrauterine live fetus with ultrasound after 12 weeks of gestation. DISCUSSION: This is the first study protocol to investigate the efficacy of LMWH as an adjuvant drug for IVF-FET outcomes in PCOS women, by comparing differences in ongoing pregnancy rate, clinical pregnancy rate, live birth rate, and early pregnancy loss rate between LMWH group and the control group. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000036527. Registered on August 24, 2020.

Sperm DNA fragmentation index affect pregnancy outcomes and offspring safety in assisted reproductive technology.

The role of sperm DNA fragmentation index (DFI) in investigating fertility, embryonic development, and pregnancy is of academic interest. However, there is ongoing controversy regarding the impact of DFI on pregnancy outcomes and the safety of offspring in the context of Assisted Reproductive Technology (ART). In this study, we conducted an analysis of clinical data obtained from 6330 patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at the reproductive medical center of The First People's Hospital of Shangqiu and The Affiliated Hospital of Zhengzhou University. The patients was stratified into two distinct groups: IVF group and ICSI group, Within each group, patients were further classified into three subgroups. IVF: group A (< 15%) included 3123 patients, group B (15-30%) included 561 patients, and group C (≥ 30%) included 46 patients. ICSI: group A (< 15%) included 1967 patients, group B (15-30%) included 462 patients, and group C (≥ 30%) included 171 patients. Data were collected and subjected to statistical analysis. There were no significant differences in the basic characteristics among the three groups, and the sperm DFI did not significantly affect the fertilization rates, pregnancy rates, stillbirth rates and the number of birth defects. However, the incidences of miscarriage rates in IVF/ICSI groups with DFI > 30% and DFI 15-30% were significantly higher than those in IVF/ICSI groups with DFI < 15%, and the miscarriage rates in ICSI group with DFI > 30% were significantly higher than DFI 15-30% group, the smooth fitting curve shows that there is a positive correlation between miscarriage rates and sperm DFI (OR 1.095; 95% CI 1.068-1.123; P < 0.001). The birth weight of infants in the IVF/ICSI groups with DFI > 30% and DFI 15-30% exhibited a statistically significant decrease compared to those in the IVF/ICSI groups with DFI < 15%. Furthermore, the birth weight of infants in the ICSI group with DFI > 30% was lower than that of the DFI 15-30% group. The smooth fitting curve analysis demonstrates a negative association between birth weight and sperm DFI (OR 0.913; 95% CI 0.890-0.937; P < 0.001). Sperm DFI has an impact on both miscarriage rates and birth weight in assisted reproductive technology. The smooth fitting curve analysis reveals a positive correlation between miscarriage rates and DFI, while a negative correlation is observed between birth weight and DFI.

An immune window of opportunity to prevent spontaneous abortion: prepregnancy peripheral leukocytes and subsets were associated with a decreased risk of spontaneous abortion.

STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.