Miscarriage Research Articles

Trophectoderm biopsy is associated with lower risks of moderate to extreme prematurity and low birthweights: a national registry cohort study of singleton livebirths from frozen-thawed blastocyst transfers

BackgroundTrophectoderm biopsy has become the mainstay assisted reproductive technique performed for preimplantation genetic testing, accounting for 43.8% of embryo transfer cycles in the US in 2019 alone. Despite its prevalence, data on the obstetric and perinatal outcomes post trophectoderm biopsy remains sparse and mixed. ObjectiveThis study aimed to examine the risks of adverse perinatal outcomes in birth weights and prematurity after transfers of vitrified-thawed blastocyst with trophectoderm biopsy for preimplantation genetic testing. Study DesignThis was a retrospective observational cohort study of 45,712 singleton live births resulting from autologous vitrified-thawed blastocyst transfer cycles with or without trophectoderm biopsy for preimplantation genetic testing, reported by participating member clinics to the Society for Assisted Reproductive Technology national registry between 2014 and 2017. Adverse perinatal outcomes of preterm births and low birth weights were analyzed. Multivariable regression analyses were performed to control for covariates. Comparing the trophectoderm biopsy (n=21,584) and no trophectoderm biopsy (n=24,128) groups, adjusted odds ratios were calculated for the outcomes of small for gestational age, large for gestational age, low birth weight < 2,500 g, very low birth weight < 1,500 g, extremely low birth weight < 1,000 g, late preterm births < 37 weeks, moderate preterm births < 34 weeks, and extremely preterm births < 28 weeks. ResultsWomen in the trophectoderm biopsy group were older and more likely to have prior pregnancies, deliveries, and history of spontaneous abortions. Tobacco use, diminished ovarian reserve, and recurrent pregnancy loss were also more prevalent in the trophectoderm biopsy group. Trophectoderm biopsy was not associated with small-for-gestational-age (aOR 0.97, 95% CI 0.85-1.12, p-value 0.72) or large-for-gestational-age newborns (aOR 1.10, 95% CI 0.99-1.22, p-value 0.09). Risks of preterm births < 37 weeks gestation were similar between the biopsy and non-biopsy groups (aOR 0.93, 95% CI 0.85-1.02, p-value 0.11). Trophectoderm biopsy was associated with a significantly lower risk of low birthweight < 2,500 g (aOR 0.80, 95% CI 0.70-0.92, p-value <0.001), very low birthweight < 1,500 g (aOR 0.62, 95% CI 0.46-0.83, p-value <0.001), extremely low birthweight < 1,000 g (aOR 0.48, 95% CI 0.31-0.74, p-value <0.001), moderate preterm birth < 34 weeks (aOR 0.76, 95% CI 0.64-0.91, p-value 0.003), and extreme preterm birth < 28 weeks (aOR 0.63, 95% CI 0.43-0.92, p-value 0.017). ConclusionTrophectoderm biopsy is not associated with increased risks of small for gestational age, large for gestational age, or late preterm birth. Risks of low birthweight, very low birthweight, and extremely low birthweight from moderate and extreme preterm births are lower after trophectoderm biopsy, possibly by selecting against confined placental mosaicism or inducing placental epigenetic changes, the mechanisms of which warrant further investigation.

Reproductive health among women of child-bearing age after surgery for rheumatic heart disease in Rwanda

ObjectiveTo determine maternal and fetal outcomes in postoperative women with rheumatic heart disease who become pregnant after valve surgery and evaluate current anticoagulation management during pregnancy. MethodsData from the Rwandan rheumatic heart disease cardiac surgical registry identified all female patients who underwent valve surgery before or during childbearing age since 2006. In total, 136 participants completed a mixed-methods questionnaire detailing each pregnancy after surgery, including anticoagulation regimen and outcomes. ResultsWe found that 38.2% (n = 136) of patients reported at least 1 pregnancy after surgery, of which more than one half were unintentional (53.9%, n = 52). Among those patients with mechanical valves, most remained on warfarin alone during pregnancy (58.5%, n = 53) whereas one third were switched to low molecular weight heparin during the first, second, or third trimesters (5 vs 4 vs 7, n = 18). Women with bioprosthetic valve replacement or valve repair were more likely to experience live term births (84.6% vs 45.3%, P < .01) and less likely to report spontaneous abortion (3.9% vs 30.2%, P < .01) compared with women with mechanical valve replacement. Excessive bleeding was the most common complication during pregnancy (9.1%, n = 79), and 2 infants were diagnosed with congenital defects associated with warfarin embryopathy (4.8%, n = 42). ConclusionsDespite preoperative counseling discouraging conception, many women with prosthetic valves still become pregnant after surgery. The results of this study will inform evidence-based and context-specific practices for anticoagulation during pregnancy in Rwanda and the region.

Moderating Role of Sense of Coherence on the Relationship between Grief and Embitterment among Women's Experiences Fetal Demise/Spontaneous Abortion

A time of anticipation and support, bearing a child is an emotional journey defined by the promise and certainty of new life. However, some individuals and couples have a deep and often tragic experience in the middle of this joy and expectation: fetal demise/ spontaneous abortion. The intention of the current study is to examine the association between grief and embitterment for females who have undergone fetal demise/ spontaneous abortion. The study also aims to explore the buffering impact of a sense of coherence on the association between grief and embitterment. Data from 200 married women who experienced fetal demise/ spontaneous abortion was collected in person and online by using a purposive sampling technique. For data collection, three reliable scales were used, namely the Perinatal Grief Scale (PGS) for grief, the Traumatic Embitterment Disorder Self-Rating Scale (PTED) for embitterment, and the Sense of Coherence (SOC) scale for measuring sense of coherence. Results of the study suggest a positive relationship between grief and embitterment. As grief increases, embitterment also increases. Sense of Coherence helps to decrease the impact of embitterment. Sense of Coherence significantly moderates the association between grief and embitterment. The study implications were examined.

Association of Maternal Serum Vitamin D Level with Hydatidiform Mole-A Systemic Review

Hydatidiform mole is an abnormal type of pregnancy, in which a potentially anomalous ovum is abnormally fertilized resulting in a subsequently non-viable conceptus becoming an enlarged growth in the uterus with dangerous complications. These moles can occur as either complete or partial, each with its own unique features. Like other risk factor, nutritional risk factors are associated with increased likelihood of development of HM. Low dietary intake of carotene, inadequate protein and animal fats are thought to be associated with increased risk of HM. Vitamin D is a steroid hormone with receptors found throughout the body including ovary, uterus, and placenta and has natural immunomodulator with anti-inflammatory properties. At the ovarian level, vitamin D has been shown to enhance ovulation. In the human syncytiotrophoblast, vitamin D and its components act together to enhance the expressions of human chorionic gonadotropin (hCG), human placental lactogen, estrogen and progesterone. Furthermore, vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues and 1,25(OH)2D3 also inhibits angiogenesis and metastasis. Deficiency of vitamin D may lead to increased ROS and decreased antioxidative defense systems that could lead to oxidative injury in patients with HM. In the human syncytiotrophoblast, vitamin D and its components act together to enhance the expressions of human chorionic gonadotropin (hCG), human placental lactogen, estrogen and progesterone. Furthermore, vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues and 1,25(OH)2D3 also inhibits angiogenesis and metastasis. Deficiency of vitamin D may lead to increased ROS and decreased antioxidative defense systems that could lead to oxidative injury in patients with HM. Studies showed there is significant association of low vitamin D level and obstetric complications like early pregnancy loss, premature rupture of membrane, fetal growth restriction and also many extra-skeletal diseases like ovary and colon cancer. In developing countries like-Bangladesh, vitamin D deficiency is much more common and starting in early life and persisting across the life span due to limited exposure to sunlight and low consumption of animal sources food. Therefore, this study was intended to determine the association of vitamin D and hydatidiform mole in a Bangladeshi woman, which may help in deciding about vitamin D supplementation as a preventive measure of hydatidiform mole.

Influence of Nutrition Management Education on Mothers Knowledge and Attitudes in Fulfilling Nutrition for Obese Pregnant Women

Obesity is a high obstetric risk increasing the risk of maternal and fetal morbidity and death. Complications that can occurred in pregnant women with obesity are an increased risk of hypertension, gestational diabetes, spontaneous abortion, and postpartum hemorrhage. This research aims to determine the effect of nutritional management education on mothers knowledge and attitudes in fulfilling nutritional needs of obese pregnant women. The study used a quasi-experiment with a pre-test and post-test with a control group design. The sample in this study was 60 obese pregnant women who were divided into an intervention group and a control group, each with 30 respondents. The instruments used were observation sheets and nutritional management menu lists. Data analysis used the Mann-Whitney test with a significance level of p ≤ 0.05. The study showed a significant difference between knowledge (p-value=0.015) and mothers' attitudes towards fulfilling nutrition (p-value=0.011) before and after nutrition management education. Nutrition management education is critical to improving nutritional fulfilment for pregnant women.

The Success of Mifepristone and Misoprostol in the Management of Early Pregnancy Loss at a Community Hospital: A Prospective Study

ObjectivesThis prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL). MethodsWe recruited 441 participants; 188 met the eligibility criteria. Participants were 18 years of age and older who experienced a confirmed EPL (<12 weeks gestational age) defined by an intrauterine pregnancy with a non-viable embryonic or anembryonic gestational sac with no fetal heart activity. Participants were given 200 mg of mifepristone pre-treatment orally followed by 2 doses of misoprostol 800 μg vaginally after 24 and 48 hours. Participants were seen in follow-up on day 14 to confirm the absence of a gestational sac, classified as treatment success. For failed treatment (defined by retained gestational sac), we offered expectant management or a third dose of misoprostol and/or dilatation and curettage. We followed all participants for 30 days. We collected data on overtreatment for retained products of conception and hospital admissions for adverse events. ResultsOverall, 181 participants followed the protocol and 169 (93.3%) participants had a complete expulsion of the gestational sac by the second visit (day 14). Twelve (6.6%) failed the treatment and 1 had an adverse event of heavy vaginal bleeding requiring dilatation and curettage. Despite the expulsion of the gestational sac, 29 cases (17.1%) at subsequent follow-up were diagnosed as retained products of conception based on ultrasound assessment of thickened endometrium. ConclusionsPretreatment with mifepristone followed by 2 doses of misoprostol with a 14-day follow-up resulted in a high expulsion rate and is a safe management option for EPL.

Seroprevalence and Risk Factors of Toxoplasmosis in Female Students from Northwest Iran

Background: Toxoplasmosis is a significant zoonotic disease caused by the protozoan parasite Toxoplasma gondii. This infection can have dire consequences if it occurs during pregnancy, as it may result in spontaneous abortion or congenital disorders. Using serological methods, we investigated the seroprevalence of Toxoplasma infection in female students of childbearing age and also determined the association between Toxoplasma infection and pregnancy. Methods: In this cross-sectional study, blood samples were collected from female students of childbearing age from three provinces in northwest Iran who studied at Maragheh University of Medical Sciences. Anti-Toxoplasma IgG and IgM antibodies were identified by ELISA and ELFA methods, and the relationship between Toxoplasma infection, demographic characteristics, and risk factors was evaluated. Results: The ELISA and ELFA serology test results for measuring IgG and IgM, were similar. One hundred cases (28.73%) were positive for Toxo IgG, and 6 cases (1.72%) were positive for Toxo IgM. The results showed that some risk factors, such as contact with cats and activities, such as agriculture or contact with soil, were significantly (P&lt;0.05) related to T. gondii seropositivity. Conclusion: More than 70% of the childbearing-age female students studied in this investigation were susceptible to infection during pregnancy, and the performance of regular serological testing during pregnancy and health education about toxoplasmosis before and after gestation is essential to prevent congenital toxoplasmosis.

Prenatal Management of High Risk Fetal Sacrococcygeal Teratoma

Introduction: Fetal sacrococcygeal teratomas (SCGT), the most common fetal neoplasm diagnosed in fetuses, are a rare condition with an estimated incidence of 1 in 40,0000 live births. Fetal SCGT is usually suspected when characteristic findings are seen on ultrasound such as a mass that is cystic and/or solid and is located in the sacral region. MRI may also be used to more accurately characterize the tumor and to help distinguish between SCGTs and distal neural tube defects like sacral meningomyelocele. Despite advances in ultrasound and MRI, only approximately 50% are diagnosed prenatally. The detection of fetal SCGT is important because it changes pregnancy monitoring and management as it is associated with fetal hydrops, intrauterine death, polyhydramnios, mirror syndrome, and mortality rates as high as 43%. Once an SCGT has been identified, serial ultrasound evaluation of the fetus, placenta, and SCGT is important to identify early signs of fetal hydrops, fetal anemia, or cardiac failure and to intervene as appropriate. Case Report: A 40-year-old G5P4004 was referred to Maternal Fetal Medicine (MFM) due to findings of a 1 cm mass near the fetal bladder on first trimester ultrasound. She had a level II ultrasound performed by MFM at 16.2 weeks where a 3.6 x 2.3 x 2.6 cm mass was identified. This mass was adjacent to the sacrococcygeal region. Due to its location and characteristic appearance, with both cystic and solid components with high vascularity, a fetal sacrococcygeal teratoma was suspected. There were no signs of hydrops or fetal anemia. At this time, the recommendation for management was: ultrasounds every 2 weeks to assess for hydrops and fetal anemia, growth ultrasound every 4 weeks, an echocardiogram by pediatric cardiology at 22-24 weeks, a fetal MRI at 28 weeks, and delivery between 37-39 weeks or earlier pending clinical course. At 24.2 weeks, she developed polyhydramnios with a maximum vertical pocket (MVP) of 10.5 cm. She had also failed her 1-hour glucose tolerance test with a value of 287 mg/dL. Due to the new finding of polyhydramnios and diagnosis of gestational diabetes, her monitoring was increased to weekly, with biophysical profile (BPP) starting at 28 weeks and weekly nonstress tests (NST) at 32 weeks. A fetal MRI was performed at 26.4 weeks and showed a large lesion extending off the sacrococcygeal region measuring 9.6 x 6.3 x 7.7 cm that was composed of both solid and cystic components. By 32.2 weeks, she developed severe polyhydramnios with an AFI of 36.0 cm and accelerated fetal growth due to an AC &gt; 99th percentile. The last ultrasound she had at 34.2 weeks the SCGT measured 17.7 x 13.3 x 13.6 cm and severe polyhydramnios persisted. The patient went into preterm labor at 35.2 weeks and had a cesarean section due to known SCGT measuring greater than 5 cm. Immediately after delivery, the neonate was evaluated by the neonatal team and transferred to the Neonatal Intensive Care Unit. The infant had surgical resection of the mass and will have tumor markers, AFP and LDH, monitored for development of recurrent immature or mature teratoma. The pathology report confirmed the diagnosis for benign sacrococcygeal teratoma. Discussion: Failure to diagnose a fetal sacrococcygeal teratoma has potentially catastrophic consequences for the fetus and mother. Maternal complications include hyperemesis, preeclampsia, mirror syndrome, preterm labor, and HELLP syndrome. Significant obstetric complications can be as high as 81%. Intrauterine fetal complications include fetal hydrops from high-output failure, fetal anemia, intratumoral hemorrhage, polyhydramnios, genitourinary obstruction leaking to hydronephrosis and or hydroureter. SCGT size &gt;10 cm or tumor with rapid growth has &gt; 50% perinatal mortality. Tumor characteristics associated with higher mortality rates are early diagnosis, solid components, high vascularity, tumor size &gt; 10 cm, and rapid growth &gt; 150 cm3/week. Another way to risk stratify these patients is by calculating a tumor volume to fetal weight ratio (TFR), which if &gt; 0.12 at &lt; 24 weeks is predictive of an overall poor prognosis. When comparing this case to literature review of sacrococcygeal teratomas, the patient’s fetal SCGT would be classified as high risk of mortality due to the tumor characteristics of early diagnosis, TFR at 20 weeks being 0.16, large size, rapid growth, and pronounced vascularity. Overall, in this high risk case of SCGT, the close follow up and evidence-based management with utilization and collaboration of a multidisciplinary team including Maternal Fetal Medicine, NICU, and Pediatric Surgery in a tertiary center resulted in a successful outcome.

Prenatal Management of High Risk Fetal Sacrococcygeal Teratoma

Introduction: Fetal sacrococcygeal teratomas (SCGT), the most common fetal neoplasm diagnosed in fetuses, are a rare condition with an estimated incidence of 1 in 40,0000 live births. Fetal SCGT is usually suspected when characteristic findings are seen on ultrasound such as a mass that is cystic and/or solid and is located in the sacral region. MRI may also be used to more accurately characterize the tumor and to help distinguish between SCGTs and distal neural tube defects like sacral meningomyelocele. Despite advances in ultrasound and MRI, only approximately 50% are diagnosed prenatally. The detection of fetal SCGT is important because it changes pregnancy monitoring and management as it is associated with fetal hydrops, intrauterine death, polyhydramnios, mirror syndrome, and mortality rates as high as 43%. Once an SCGT has been identified, serial ultrasound evaluation of the fetus, placenta, and SCGT is important to identify early signs of fetal hydrops, fetal anemia, or cardiac failure and to intervene as appropriate. Case Report: A 40-year-old G5P4004 was referred to Maternal Fetal Medicine (MFM) due to findings of a 1 cm mass near the fetal bladder on first trimester ultrasound. She had a level II ultrasound performed by MFM at 16.2 weeks where a 3.6 x 2.3 x 2.6 cm mass was identified. This mass was adjacent to the sacrococcygeal region. Due to its location and characteristic appearance, with both cystic and solid components with high vascularity, a fetal sacrococcygeal teratoma was suspected. There were no signs of hydrops or fetal anemia. At this time, the recommendation for management was: ultrasounds every 2 weeks to assess for hydrops and fetal anemia, growth ultrasound every 4 weeks, an echocardiogram by pediatric cardiology at 22-24 weeks, a fetal MRI at 28 weeks, and delivery between 37-39 weeks or earlier pending clinical course. At 24.2 weeks, she developed polyhydramnios with a maximum vertical pocket (MVP) of 10.5 cm. She had also failed her 1-hour glucose tolerance test with a value of 287 mg/dL. Due to the new finding of polyhydramnios and diagnosis of gestational diabetes, her monitoring was increased to weekly, with biophysical profile (BPP) starting at 28 weeks and weekly nonstress tests (NST) at 32 weeks. A fetal MRI was performed at 26.4 weeks and showed a large lesion extending off the sacrococcygeal region measuring 9.6 x 6.3 x 7.7 cm that was composed of both solid and cystic components. By 32.2 weeks, she developed severe polyhydramnios with an AFI of 36.0 cm and accelerated fetal growth due to an AC &gt; 99th percentile. The last ultrasound she had at 34.2 weeks the SCGT measured 17.7 x 13.3 x 13.6 cm and severe polyhydramnios persisted. The patient went into preterm labor at 35.2 weeks and had a cesarean section due to known SCGT measuring greater than 5 cm. Immediately after delivery, the neonate was evaluated by the neonatal team and transferred to the Neonatal Intensive Care Unit. The infant had surgical resection of the mass and will have tumor markers, AFP and LDH, monitored for development of recurrent immature or mature teratoma. The pathology report confirmed the diagnosis for benign sacrococcygeal teratoma. Discussion: Failure to diagnose a fetal sacrococcygeal teratoma has potentially catastrophic consequences for the fetus and mother. Maternal complications include hyperemesis, preeclampsia, mirror syndrome, preterm labor, and HELLP syndrome. Significant obstetric complications can be as high as 81%. Intrauterine fetal complications include fetal hydrops from high-output failure, fetal anemia, intratumoral hemorrhage, polyhydramnios, genitourinary obstruction leaking to hydronephrosis and or hydroureter. SCGT size &gt;10 cm or tumor with rapid growth has &gt; 50% perinatal mortality. Tumor characteristics associated with higher mortality rates are early diagnosis, solid components, high vascularity, tumor size &gt; 10 cm, and rapid growth &gt; 150 cm3/week. Another way to risk stratify these patients is by calculating a tumor volume to fetal weight ratio (TFR), which if &gt; 0.12 at &lt; 24 weeks is predictive of an overall poor prognosis. When comparing this case to literature review of sacrococcygeal teratomas, the patient’s fetal SCGT would be classified as high risk of mortality due to the tumor characteristics of early diagnosis, TFR at 20 weeks being 0.16, large size, rapid growth, and pronounced vascularity. Overall, in this high risk case of SCGT, the close follow up and evidence-based management with utilization and collaboration of a multidisciplinary team including Maternal Fetal Medicine, NICU, and Pediatric Surgery in a tertiary center resulted in a successful outcome.

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

BackgroundMultiple empirical investigations have indicated a connection between asthma and adverse pregnancy outcomes (APOs). Nevertheless, the effects of asthma on APOs remain uncertain. MethodsWe performed bi-directional Univariable Mendelian randomization (UVMR) analyses using combined information obtained from genome-wide association studies (GWAS) data that is publicly accessible. The principal approach used to analyze the causal association between asthma or age when diagnosed and APOs was the inverse variance weighted (IVW) method. The two types of data regarding exposure originate from the IEU Open GWAS project, which includes 56,167 and 47,222 European asthma patients, respectively. The data of four APOs were acquired via the GWAS dataset of the FinnGen collaboration. In addition, we implemented multivariable Mendelian randomization (MVMR), controlling for confounding factors such as smoking status, frequent drinking, body mass index (BMI), and live birth quantity. Furthermore, we executed several meticulous sensitivity studies to ascertain the reliability of our MR results. ResultsFollowing the implementation of the Bonferroni adjustment, the UVMR assessment revealed that in the IVW model, asthma was significantly linked to an elevated risk of spontaneous abortion (SA) (odds ratio [OR]: 1.115; 95 % confidence interval [CI]: 1.031–1.206; P = 0.006) and gestational diabetes mellitus (GDM) (OR: 1.125; 95 % CI: 1.037–1.220; P = 0.005). However, there was no causal correlation between asthma and preterm birth (PTB) (OR: 0.979; 95 % CI: 0.897–1.068; P = 0.629) or preeclampsia (PE) (OR: 1.059; 95 % CI: 0.951–1.179; P = 0.297). After adjusting for confounding factors, including smoking status, frequent drinking, BMI, and live birth quantity, the MVMR analysis shows a statistically significant causal relationship between asthma and SA or GDM. Furthermore, our investigation's findings did not reveal a substantial correlation between the age of asthma onset based on genetics and the likelihood of SA or GDM. The inverse MR outcomes indicate a lack of causal connection linking APOs to the incidence of asthma. The validity of these findings were verified by sensitivity analyses. ConclusionsThe evidence provided by this study proves that genetically determined asthma is linked to a higher likelihood of SA and GDM. Further research is required to examine potential pathways. However, no conclusive evidence has been found to support the increased risk of SA and GDM in early asthma diagnosis or the interaction between asthma and PTB or PE, indicating that confounding factors may affect the results of previous observational studies.

Effects of COVID-19 Infection on Fetal Growth in Pregnancy

Background: Infections are known to affect fetal development and growth. Studies have shown that there is a higher frequency of maternal vascular malperfusion in the placental bed in pregnant women infected with COVID-19. It is further suggested that the abovementioned changes seen in the placentas of women infected with COVID-19 is associated with significant clinical sequelae, such as, preterm birth, fetal growth restriction (FGR), and fetal demise. Although there are growing studies that have evaluated the impact of COVID-19 infection on fetal growth, data remains limited. As a result, there is little consensus on perinatal recommendations and counseling that should be given to women infected patients COVID-19 during pregnancy. During the COVID-19 pandemic, our Maternal Fetal Medicine Clinics opted to perform serial growth ultrasounds and additional antenatal testing in the third trimester in women infected with the disease. Whether performance of these ultrasounds identified cases of fetal growth restriction and impacted fetal outcomes remains unknown. The purpose of this study is to perform a retrospective review of all ultrasounds performed in women identified to have COVID-19 during June 2020-December 2022, and to evaluate the impact on fetal growth. We hypothesize that COVID-19 will increase the risk of fetal growth restriction compared to pregnant women without COVID-19. Study Design: This is a retrospective cohort study within the Obstetrix Maternal-Fetal Medicine Specialist of Houston Clinics. The study included all patients aged 16-55 years old with a singleton pregnancy who received an ultrasound at Obstetrix Maternal-Fetal Medicine Specialist of Houston between June 2020-December 2022. COVID-19 infection during pregnancy was defined as a self-reported positive SARS-Co-2 RT-PCR or Rapid Test. FGR was defined as estimated fetal weight less than the 10% or abdominal circumference less than the 10% for gestational age. Maternal and fetal characteristics, including FGR, were collected and compared between the two groups. Results: Among the 21,917 women with a singleton pregnancy who received an ultrasound at Obstetrix Maternal-Fetal Medicine Specialist of Houston between June 2020-December 2022, 484 (2%) had COVID-19 infection during pregnancy and 21,433 (98%) did not. Of those who had COVID-19 infection during pregnancy there were 45 (9%) cases of FGR, and when compared to pregnant individuals reporting negative for COVID-19 there were 2,928 (14%) cases of FGR, p=005. When the 484 women who had COVID-19 were stratified by the timing of their COVID-19 infection by first, second and third trimester, there was no significant difference in the proportion who had an offspring with FGR (p=0.33 Cochran-Armitage test for trend). Conclusion: COVID-19 infection in pregnancy, when compared to those who do not have COVID-19 infection in pregnancy does not appear to be more associated with FGR. The performance of routine serial fetal growth ultrasounds may not be indicated in pregnant women solely for the purpose of having a history of a COVID-19 infection during pregnancy.

Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.

The corpus callosum is one of the five main cerebral commissures. It is key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). The corpus callosum dys- or agenesis is a rare disease (1:4000 live births), but it can have serious mental effects. In our study, we processed the data of 64 pregnant women. They attended a prenatal diagnostic center and genetic counseling from 2005 to 2019 at the Department of Obstetrics and Gynecology at Semmelweis University. The pregnancies had the following outcomes: 52 ended in delivery, 1 in spontaneous abortion, and 11 in termination of pregnancy (TOP) cases (n = 64). The average time of detection with imaging tests was 25.24 gestational weeks. In 16 cases, prenatal magnetic resonance imaging (MRI) was performed. If the abnormality was detected before the 20th week, a genetic test was performed on an amniotic fluid sample obtained from a genetic amniocentesis. Karyotyping and cytogenetic tests were performed in 15 of the investigated cases. Karyotyping gave normal results in three cases (46,XX or XY). In one of these cases, postnatally chromosomal microarray (CMA) was later performed, which confirmed Aicardi syndrome (3q21.3-21.1 microdeletion). In one case, postnatally, the test found Wiedemann-Rautenstrauch syndrome. In other cases, it found X ring, Di George syndrome, 46,XY,del(13q)(q13q22) and 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards syndrome was diagnosed in six cases, and Patau syndrome in one case. We found that corpus callosum abnormalities are often linked to chromosomal problems. We recommend that a cytogenetic test be performed in all cases to rule out inherited diseases. Also, the long-term outcome does not just depend on the disease's severity and the associated other conditions, and hence proper follow-up and early development are also key. For this reason, close teamwork between neonatology, developmental neurology, and pediatric surgery is vital.

MERCURY EXPOSURE AND HUMAN REPRODUCTIVE HEALTH (LITERATURE REVIEW)

Mercury (Hg), a highly toxic environmental pollutant, which hazards for human health, including to reproductive system, fertility and pregnancy outcome. Research has shown that Hg could induce impairments in the reproductive function due to cellular deformation of the Leydig cells and the seminiferous tubules, testicular degeneration and degenerative atresia of primordial and primary follicles as well as diminishes the steroidogenesis and synthesis of sex hormones. Some studies investigated miscarriage, spontaneous abortions, stillbirth, and low birth weight due to occupational Hg exposure. This review evaluates the hypothesis that exposure to Hg may. This review evaluates the hypothesis that chronic exposure to mercury can increase the risk of reduced fertility, spontaneous abortion and congenital deficits or abnormalities.

Clinical outcomes of fresh and frozen embryos transfer after in vitro fertilization in spouses of patients with severely low sperm concentration and motility.

To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer (IVF-ET) with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility. A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center, Sir Run Run Shaw Hospital from April 2018 to April 2022. After applying the propensity score matching (PSM), 473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study, and the pregnancy and neonatal outcomes were compared between the two groups. There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups (all P>0.05). In the stratification analysis, the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group (P<0.05), but the very early pregnancy loss rates were similar between the two groups (P>0.05), while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group (P<0.05). Among different age groups of women, the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to <30 years old group than that in the 30 to <35 years old group (both P<0.05), but the clinical pregnancy rate was lower in the 20 to <30 years old group than that in the 30 to <35 years old group (P>0.05). Additionally, the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to <30 years age group (P<0.05). There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET. Due to the shorter transfer times, less embryo freezing damage and reduced costs, fresh embryo transfer can be considered as the first choice. However, it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation

BackgroundThyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid‐treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known.AimsTo determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes.Materials and MethodsProspective cohort study involving 46 euthyroid (anti‐thyroid peroxidase antibody negative) and 16 levothyroxine‐replaced women with baseline thyroid‐stimulating hormone (TSH) &lt;2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick‐up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared.ResultsMedian serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine‐replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine‐replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ.ConclusionAdequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Possible adverse events of imidazole antifungal drugs during treatment of vulvovaginal candidiasis: analysis of the FDA Adverse Event Reporting System

Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.

Influence of COVID-19 infection on early pregnancy outcomes in different periods around frozen embryo transfer

PurposeThe study aimed to investigate the potential influence of COVID-19 infection on embryo implantation and early development in women undergoing frozen embryo transfer (FET), with a specific focus on infections occurring at different periods around FET.MethodsA retrospective analysis was performed on women who had undergone FET during a period marked by a significant surge in COVID-19 infection in Shanghai. All enrolled women experienced their first documented COVID-19 infection around the time of FET, ensuring that infections did not occur prior to oocyte retrieval. Participants were categorized into six groups based on the timing of infection: uninfected, ≥ 60 days, < 60 days before FET, 0–14 days, 15–28 days, and 29–70 days after FET. Clinical outcomes were compared across these groups.ResultsThe infection rate among the total of 709 cases was 78.28%. Infected individuals exhibited either asymptomatic or mild symptoms. The ongoing pregnancy rates for the first four groups were 40.7%, 44.4%, 40.5%, and 34.2% (P = 0.709) respectively, biochemical pregnancy rates (59.1% vs. 61.1% vs. 67.6% vs. 55.7%, P = 0.471) and clinical pregnancy rates (49.6% vs. 55.6% vs. 55.4% vs. 48.1%, P = 0.749), all showed no significant differences. Early spontaneous abortion rates across all six groups were 18.3%, 20.0%, 25.0%, 28.9%, 5.4%, and 19.0% respectively, with no significant differences (P = 0.113). Multivariable logistic analysis revealed no significant correlation between the infection and ongoing pregnancy.ConclusionAsymptomatic or mild COVID-19 infections occurring around FET do not appear to have a significant adverse impact on early pregnancy outcomes.

Micronutrients in Adverse Pregnancy Outcomes

About 10 to 20% of reported pregnancies have complications like spontaneous abortion (SA), preeclampsia (PE), preterm birth (PTB), and fetal growth restriction (FGR); 60% are attributed to maternal nutritional alterations. Multiple micronutrients (MMN) are supplemented in the antenatal period, but no proper validation/guidelines are available regarding dosing/time, the need for initiation, and the duration of supplementation. Studies have reported adverse pregnancy complications related to the overuse/unwanted use of multiple micronutrient supplementations during pregnancy. Identifying the exact population requiring supplementation is necessary to prevent its abuse. This article attempts to review the impacts of micronutrient deficiency/supplementation in cases of SA, FGR, and gestational diabetes mellitus (GDM), preterm delivery and PE. The study used a literature search using PubMed, Google Scholar, Mendeley, and Scopus Databases using search words pregnancy, spontaneous abortion, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), preterm delivery, preeclampsia (PE) or “adverse pregnancy” associated with minerals, micronutrients, or supplementation. The review also considered in-house literature databases, a single-window search at Kasturba Medical College (KMC) Health sciences library, MAHE (Manipal Academy of Higher Education). The figures included in the study were created by Biorender.com. Micronutrients play multiple roles during pregnancy and fetoplacental growth stimulating growth hormone secretion, Lysyl oxidase (LOX), involved in the crosslinking between collagen and elastin in the amniotic membrane, downregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, Il-10, IL-12, tumor necrosis factor (TNF)-alpha and several chemokines involved in hypertension, immune-inflammatory pathways, attenuate insulin resistance, structural development of neurons and glia. Over-supplementation has led to complications such as spontaneous abortion and gestational diabetes mellitus. Since there is a lack of standardization concerning micronutrient supplementation during pregnancy, there is a need for systematic study related to the role of micronutrients during each trimester of pregnancy to optimize its supplementation and to prevent hazards associated with its abuse.

First Trimester Abortion and Psychiatric Morbidity.

Early pregnancy loss is a traumatic event following which clients may experience psychological morbidities. Mental illness is associated with multiple obstetric and social factors surrounding the period of pregnancy loss. The aim of this study was to find the prevalence of depression and anxiety before and after undergoing spontaneous or induced first trimester abortion and to analyze demographic and obstetric factors associated with it. This is an observational study conducted as Kathmandu Medical College (KMC) for a duration of one year from September 2022 to August 2023. All clients with abortion were screened for psychiatric morbidity using the The Hospital Anxiety and Depression Scale (HADS). Each client was assessed at first hospital visit and then at two weeks and two months following abortion. Level of anxiety and depression was analyzed in relation to socio-demographic factors and the type of abortion. 171 clients with pregnancy loss were enrolled. Pre-abortion, severe anxiety was present in 6(13%) clients with spontaneous abortion. Pre-abortion, mild to severe anxiety was present in 31 (67.3%) clients and at two weeks and two months in 11 (23.9%) and 11 (23.9%) clients respectively. In clients undergoing induced abortion, varying levels of anxiety was present in 54(43.2%) pre-abortion, and 48(38.4%) and 54(43.2%) clients at two weeks and two months. Mild to moderate depression was seen in 21 (45.6%) among spontaneous abortion and 51 (40.8%) clients among induced abortion. Mean score on HADS decreased with time. Anxiety and depression were common following early pregnancy loss. Rate of anxiety seems to decrease with time in spontaneous abortion but in induced abortion it remains persistent. Rate of depression tends to decrease with time for both types of abortion.

Association between Group B Streptococcus and Clinical Chorioamnionitis by Gestational Week at Delivery-A Multicenter Cohort Study.

In the era of group B Streptococcus (GBS) screening and intrapartum antibiotic prophylaxis (IAP), GBS colonization has been associated with a lower risk of chorioamnionitis, possibly due to a protective effect of IAP. We sought to confirm this finding and assess whether this association varies by gestational week at delivery. We performed a retrospective cohort study of term (37.0-42.6 weeks), singleton parturients with known GBS status who delivered from 2005 to 2021 at two academic medical centers in Israel. We excluded patients who underwent planned cesarean, out of hospital birth, or had a fetal demise. Patients received GBS screening and IAP for GBS positivity as routine clinical care. The primary outcome was a diagnosis of clinical chorioamnionitis as determined by the International Classification of Diseases 10th Revision code, compared between GBS-positive and -negative groups, and assessed by gestational week at delivery. Of 292,126 deliveries, 155,255 met inclusion criteria. In total, 30.1% were GBS positive and 69.9% were negative. GBS-positive patients were 21% less likely to be diagnosed with clinical chorioamnionitis than GBS-negative patients, even after controlling for confounders (1.5 vs. 2.2%, adjusted odds ratio: 0.79, 95% confidence interval: 0.68-0.92). When assessed by gestational week at delivery, there was a significantly greater difference in rates of clinical chorioamnionitis between GBS-positive versus GBS-negative groups with advancing gestational age: 1.5-fold difference at 38 to 40 weeks, but a twofold difference at 42 weeks. The risk of clinical chorioamnionitis remained stable in the GBS-positive group, but increased significantly in the GBS-negative group at 41- and 42-week gestation (2.0 vs. 2.9%, p < 0.01 at 41 weeks; up to 3.9% at 42 weeks, p < 0.01). In a large multicenter cohort with universal GBS screening and IAP, GBS positivity was associated with a lower risk of chorioamnionitis, driven by an increasing rate of chorioamnionitis among GBS-negative patients after 40 weeks. · GBS positivity and IAP may be associated with lower risk of chorioamnionitis.. · GBS-positive patients were less likely to be diagnosed with chorioamnionitis.. · This difference increased with advancing gestational age after 40 weeks..