Intrauterine insemination timing models-LH can only take you so far.

RESEARCH QUESTION: Can an optimal LH threshold algorithm accurately predict timing of ovulation for natural cycle-intrauterine insemination (NC-IUI)? DESIGN: A retrospective cohort study (2018-2022) including 2467 natural cycles. Ovulation timing for these cycles was determined using a previously developed AI model. Two LH thresholds, low and high, were determined in the LH algorithm. Being below the low threshold meant that ovulation is likely to occur in ≥ 4 days, suggesting another daily blood test. Between the two thresholds meant that ovulation was likely in 2-3 days, suggesting IUI the next day. Above the high threshold meant that ovulation will likely occur tomorrow, suggesting performing IUI on the same day. RESULTS: The optimal LH model with a high threshold of 40 mIU/ml and a low threshold of 11 mIU/ml succeeded in correctly predicting timing for IUI (day - 1, - 2 relative to ovulation) in 75.4% (95%CI 75.3-75.4). In 23.1% (95%CI 23.0-23.2), the algorithm predicted "error," suggesting performing insemination when in fact it would have been performed on a non-optimal day (0 or - 3). A previously described 3-hormone-based (LH, estradiol, progesterone) AI model performed significantly better in all parameters (93.6% success rate, 4.3 "error" rate). CONCLUSIONS: An LH threshold model, representing common practice, evaluating all possible high and low LH threshold combinations, was successful in accurately scheduling timing for IUI in only 75% of cases. Integrating all three hormones as performed in the AI model may have an advantage in accurately predicting the optimal time for IUI, over the use of LH only.

The effect of COVID-19 vaccination during IVF stimulation on cycle outcomes- a retrospective cohort study.

The effect of the mRNA-BNT162b2 vaccine administered prior to fertility treatments has been addressed in several studies, presenting reassuring results. Cycle outcomes of patients receiving the vaccine during the stimulation itself have not been previously described. This retrospective cohort study included patients who received mRNA-BNT162b2-vaccine during the stimulation of fresh IVF cycles, between January-September 2021, age matched to pre-stimulation vaccinated patients and to non-vaccinated patients. Demographics, cycle characteristics and cycle outcomes were compared between groups. A total of 132 in-treatment vaccinated patients (study group), 132 pre-treatment vaccinated and 132 non-vaccinated patients that underwent fresh IVF cycles were included. Mean time from vaccination to retrieval in the study group was 6.68 days (SD 3.74; range 0-12). Oocyte yield was similar between groups (9.35 versus10.22 and 10.05 respectively; p=0.491). A linear regression model demonstrated no effect of vaccination before or during the stimulation, on oocyte yield (p>0.999). Clinical pregnancy rates (30 % versus 30 % versus 28 %) and ongoing pregnancy rates (25 % for all groups) did not differ between groups. In a logistic regression model for clinical pregnancy rates, vaccine administration and timing of vaccination were not a significant factor. This is the first study reporting the outcome of the mRNA BNT162b2 vaccine administration during the IVF stimulation itself. The vaccine administration had no impact on fresh IVF treatment outcomes compared to pre-treatment vaccinated or non-vaccinated patients. This adds to the growing evidence of COVID-19 vaccine safety in relation to fertility treatments and enables more flexibility regarding timing of vaccine administration.

An artificial intelligence-based approach for selecting the optimal day for triggering in antagonist protocol cycles.

RESEARCH QUESTION: Can a machine-learning model suggest an optimal trigger day (or days), analysing three consecutive days, to maximize the number of total and mature (metaphase II [MII]) oocytes retrieved during an antagonist protocol cycle? DESIGN: This retrospective cohort study included 9622 antagonist cycles between 2018 and 2022. The dataset was divided into training, validation and test sets. An XGBoost machine-learning algorithm, based on the cycles' data, suggested optimal trigger days for maximizing the number of MII oocytes retrieved by considering the MII predictions, prediction errors and outlier detection results. Evaluation of the algorithm was conducted using a test dataset including three quality groups: 'Freeze-all oocytes', 'Fertilize-all' and 'ICSI-only' cycles. The model suggested 1, 2 or 3 days as trigger options, depending on the difference in potential outcomes. The suggested days were compared with the actual trigger day chosen by the physician and were labelled 'concordant' or 'discordant' in terms of agreement. RESULTS: In the 'freeze-all' test-set, the concordant group showed an average increase of 4.8 oocytes and 3.4 MII oocytes. In the 'ICSI-only' test set there was an average increase of 3.8 MII oocytes and 1.1 embryos, and in the 'fertilize-all' test set an average increase of 3.6 oocytes and 0.9 embryos was observed (P < 0.001 for all parameters in all groups). CONCLUSIONS: Utilizing a machine-learning model for determining the optimal trigger days may improve antagonist protocol cycle outcomes across all age groups in freeze-all or fresh transfer cycles. Implementation of these models may more accurately predict the number of oocytes retrieved, thus optimizing physicians' decisions, balancing workloads and creating more standardized, yet patient-specific, protocols.

Prediction of ovulation: new insight into an old challenge.

Ultrasound monitoring and hormonal blood testing are considered by many as an accurate method to predict ovulation time. However, uniform and validated algorithms for predicting ovulation have yet to be defined. Daily hormonal tests and transvaginal ultrasounds were recorded to develop an algorithm for ovulation prediction. The rupture of the leading ovarian follicle was a marker for ovulation day. The model was validated retrospectively on natural cycles frozen embryo transfer cycles with documented ovulation. Circulating levels of LH or its relative variation failed, by themselves, to reliably predict ovulation. Any decrease in estrogen was 100% associated with ovulation emergence the same day or the next day. Progesterone levels > 2 nmol/L had low specificity to predict ovulation the next day (62.7%), yet its sensitivity was high (91.5%). A model for ovulation prediction, combining the three hormone levels and ultrasound was created with an accuracy of 95% to 100% depending on the combination of the hormone levels. Model validation showed correct ovulation prediction in 97% of these cycles. We present an accurate ovulation prediction algorithm. The algorithm is simple and user-friendly so both reproductive endocrinologists and general practitioners can use it to benefit their patients.

Artificial intelligence in the service of intrauterine insemination and timed intercourse in spontaneous cycles.

OBJECTIVE: To develop a machine learning model designed to predict the time of ovulation and optimal fertilization window for performing intrauterine insemination or timed intercourse (TI) in natural cycles. DESIGN: A retrospective cohort study. SETTING: A large in vitro fertilization unit. PATIENT(S): Patients who underwent 2,467 natural cycle-frozen embryo transfer cycles between 2018 and 2022. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prediction accuracy of the optimal day for performing insemination or TI. RESULT(S): The data set was split into a training set including 1,864 cycles and 2 test sets. In the test sets, ovulation was determined according to either expert opinion, with 2 independent fertility experts determining ovulation day ("expert") (496 cycles), or according to the disappearance of the leading follicle between 2 consecutive days' ultrasound examinations ("certain ovulation") (107 cycles). Two algorithms were trained: an NGBoost machine learning model estimating the probability of ovulation occurring on each cycle day and a treatment management algorithm using the learning model to determine an optimal insemination day or whether another blood test should be performed. The estradiol progesterone and luteinizing hormone levels on the last test performed were the most influential features used by the model. The mean numbers of tests were 2.78 and 2.85 for the "certain ovulation" and "expert" test sets, respectively. In the "expert" set, the algorithm correctly predicted ovulation and suggested day 1 or 2 for performing insemination in 92.9% of the cases. In 2.9%, the algorithm predicted a "miss," meaning that the last test day was already ovulation day or beyond, suggesting avoiding performing insemination. In 4.2%, the algorithm predicted an "error," suggesting performing insemination when in fact it would have been performed on a nonoptimal day (0 or -3). The "certain ovulation" set had similar results. CONCLUSION(S): To our knowledge, this is the first study to implement a machine learning model, on the basis of the blood tests only, for scheduling insemination or TI with high accuracy, attributed to the capability of the algorithm to integrate multiple factors and not rely solely on the luteinizing hormone surge. Introducing the capabilities of the model may improve the accuracy and efficiency of ovulation prediction and increase the chance of conception. CLINICAL TRIAL REGISTRATION NUMBER: HMC-0008-21.

Higher incidence of preeclampsia among participants undergoing in-vitro fertilization after fewer sperm exposures.

OBJECTIVE: Evaluation of preeclampsia (PE) incidence among participants undergoing in vitro fertilization (IVF) after various cycles of sperm donation (SD) via intrauterine inseminations (IUI) or IVF. STUDY DESIGN: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019 which included participants who conceived via IVF using SD from a single sperm bank and had a successful singleton birth at Sheba Medical Center. The study cohort was divided into two groups: Group 1 (participants who conceived via IVF after 0-1 cycles of IUI or IVF from the same sperm donor) and Group 2 (participants who conceived via IVF after 2 or more cycles of IUI or IVF from the same sperm donor). Baseline characteristics and pregnancy outcomes between the two groups were compared. In addition, a comparison between the study groups and a control of participants of the same age who conceived spontaneously and had a singleton birth at Sheba Medical Center during the same period with a record of up to two previous deliveries was done. RESULTS: A total of 228 participants conceived through IVF from SD and met the inclusion criteria. Of these, 110 were defined as Group 1 and 118 as Group 2. The participants showed no differences in their age, gravidity and parity, chronic medical conditions, or history of pregnancy complications. Preeclampsia was positively associated with Group 1 (9 [8.2%] vs. 2 [1.7%], P = 0.022). PE was observed to be more prevalent in Group 1 (P < 0.001) when compared to a control group of 45,278 participants who conceived spontaneously. No significant differences were observed in comparing Group 2 with the same control group. CONCLUSION: The incidence of PE was higher among participants who were exposed to 0-1 IUI or IVF cycles than in those who were exposed to 2 or more cycles of IUI or IVF from the same sperm donor. On comparing both groups with a control group, the incidence of PE was higher in participants who were exposed to 0-1 cycles, while there was no difference in participants exposed to 2 or more cycles. IMPLICATIONS STATEMENT: If there is a statistically significant increase in the incidence of PE when conception occurred following fewer sperm exposures, then there may be a correlation between these two. The reason for this is not entirely clear, but based on former literature, we hypothesize it may be related to the fact that repeated exposures to paternal antigens may alter the maternal immune response causing a better adaptation to the semi-allogenic nature of the fetus, its paternal half.

ABCC4 is a PGE2 efflux transporter in the ovarian follicle: A mediator of ovulation and a potential non-hormonal contraceptive target.

The role of prostaglandins (PGs) in the ovulatory process is known. However, the role of the ATP binding cassette subfamily C member 4 (ABCC4), transmembrane PG carrier protein, in ovulation remains unknown. We report herein that ABCC4 expression is significantly upregulated in preovulatory human granulosa cells (GCs). We found that PGE2 efflux in cultured human GCs is mediated by ABCC4 thus regulating its extracellular concentration. The ABCC4 inhibitor probenecid demonstrated effective blocking of ovulation and affects key ovulatory genes in female mice in vivo. We postulate that the reduction in PGE2 efflux caused by the inhibition of ABCC4 activity in GCs decreases the extracellular concentration of PGE2 and its ovulatory effect. Treatment of female mice with low dose of probenecid as well as with the PTGS inhibitor indomethacin or Meloxicam synergistically blocks ovulation. These results support the hypothesis that ABCC4 has an important role in ovulation and might be a potential target for non-hormonal contraception, especially in combination with PGE2 synthesis inhibitors. These findings may fill the gap in understanding the role of ABCC4 in PGE2 signaling, enhance the understanding of ovulatory disorders, and facilitate the treatment and control of fertility.

Treatment safety of ART cycles with extremely high oestradiol concentrations using GnRH agonist trigger.

RESEARCH QUESTION: Are IVF treatments with extremely high peak oestradiol levels and gonadotrophin releasing hormone (GnRH) agonist trigger associated with higher complication rates? DESIGN: A retrospective cohort study including patients from two large medical centres treated between 2019 and 2021. A study group with extremely high peak oestradiol levels (≥20,000 pmol/l on the day of ovarian stimulation, or ≥15,000 pmol/l on the previous day) and a control group with normal range oestradiol levels (3000-12000 pmol/l) that received GnRH agonist triggering. Patients were surveyed about complaints and medical care related to ovum retrieval and medical files were reviewed. Major complication rates and the need for medical assistance were compared. RESULTS: Several differences between the study and control group were observed because of the study design: mean age was 33.01 ± 5.14 versus 34.57 ± 4.52 (P < 0.001), mean peak oestradiol levels was 26645.34 ± 8592.57 pmol/l versus 7229.75 ± 2329.20 pmol/l (P < 0.001), and mean number of oocytes were 27.55 ± 13.46 versus 11.67 ± 5.76 (P < 0.001) for the study and control group, respectively. Major complications and hospitalization rates were similar between the study and control groups (three [1.25%] versus one [0.48%]; P = 0.62 and three [1.25%] versus two [0.96%]; P = 1.0, respectively). Thirty-six patients (15.1%) in the study group and 11 (5.3%) in the control group sought medical care after retrieval, mostly due to abdominal pain, without the need for further workup or hospitalization (P < 0.001). CONCLUSIONS: Extremely high oestradiol levels were not associated with thromboembolic events, higher major complication or hospitalization rates, and therefore may be considered safe. Nevertheless, patients may be informed of possible higher rates of discomfort, mostly abdominal pain. Larger studies are warranted to confirm our results.

Lower Sperm Exposure among Participants Undergoing Intrauterine Insemination Associated with Increased Incidence of Gestational Hypertensive Disorders.

BACKGROUND: Gestational hypertensive (GH) disorders remain a major obstetric problem. OBJECTIVES: To evaluate the incidence of gestational hypertensive disorders among participants undergoing intrauterine insemination (IUI) after exposure to various levels of sperm from sperm donation (SD). METHODS: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019. Participants conceived via IUI using SD from a single sperm bank and had a successful singleton birth. Group 1 conceived during 1-2 cycles of IUI from the same sperm donor; whereas Group 2 after 3+ cycles. RESULTS: Overall 171 patients (Group 1 = 81, Group 2 = 90) met inclusion criteria. Participants showed no differences in age, chronic medical conditions, or history of pregnancy complications. The groups differed in gravidity and parity. The factors positively associated with Group 1 included either preeclampsia or GH (11 [13.5%] vs. 1 [1.1%], P = 0.001) and GH alone (8 [9.9%] vs. 1 [1.1%], P = 0.014). Newborns from Group 1 had a statistically significant lower birth weight than those from Group 2 (3003 grams ± 564.21 vs. 3173 grams ± 502.59, P = 0.039). GH was more prevalent in Group 1 (P = 0.008) than a control group of 45,278 participants who conceived spontaneously. No significant differences were observed between Group 2 and the control group. CONCLUSIONS: The incidence of GH and preeclampsia in participants was higher among those exposed to 1-2 cycles than those exposed to 3+ cycles of IUI.

Covid-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors.

BACKGROUND: The development of covid-19 vaccinations represents a notable scientific achievement. Nevertheless, concerns have been raised regarding their possible detrimental impact on male fertility OBJECTIVE: To investigate the effect of covid-19 BNT162b2 (Pfizer) vaccine on semen parameters among semen donors (SD). METHODS: Thirty-seven SD from three sperm banks that provided 216 samples were included in that retrospective longitudinal multicenter cohort study. BNT162b2 vaccination included two doses, and vaccination completion was scheduled 7 days after the second dose. The study included four phases: T0 - pre-vaccination baseline control, which encompassed 1-2 initial samples per SD; T1, T2 and T3 - short, intermediate, and long terms evaluations, respectively. Each included 1-3 semen samples per donor provided 15-45, 75-125 and over 145 days after vaccination completion, respectively. The primary endpoints were semen parameters. Three statistical analyses were conducted: (1) generalized estimated equation model; (2) first sample and (3) samples' mean of each donor per period were compared to T0. RESULTS: Repetitive measurements revealed -15.4% sperm concentration decrease on T2 (CI -25.5%-3.9%, p = 0.01) leading to total motile count 22.1% reduction (CI -35% - -6.6%, p = 0.007) compared to T0. Similarly, analysis of first semen sample only and samples' mean per donor resulted in concentration and total motile count (TMC) reductions on T2 compared to T0 - median decline of 12 million/ml and 31.2 million motile spermatozoa, respectively (p = 0.02 and 0.002 respectively) on first sample evaluation and median decline of 9.5 × 106 and 27.3 million motile spermatozoa (p = 0.004 and 0.003, respectively) on samples' mean examination. T3 evaluation demonstrated overall recovery without. Semen volume and sperm motility were not impaired. DISCUSSION: This longitudinal study focused on SD demonstrates selective temporary sperm concentration and TMC deterioration 3 months after vaccination followed by later recovery verified by diverse statistical analyses. CONCLUSIONS: Systemic immune response after BNT162b2 vaccine is a reasonable cause for transient semen concentration and TMC decline. Long-term prognosis remains good.

The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles.

PURPOSE: To study the effect of SARS-CoV-2 infection on pregnancy rates in frozen embryo transfer (FET) cycles. METHODS: A retrospective cohort study including women under the age of 42 with documented SARS-CoV-2 infection up to 1 year prior to treatment, undergoing FET cycles in the first half of 2021, with transfer of embryos generated prior to the infection. Controls were SARS-CoV-2 non-diagnosed, non-vaccinated women matched by age, number, and day of embryo transfer. Demographic and cycle characteristics and outcomes were compared. RESULTS: Forty-one recovered women and 41 controls were included. Pregnancy rates were 29% and 49% respectively (p = 0.070). Stratification by time from SARS-CoV-2 infection to transfer into ≤ 60 and > 60 days revealed a difference in pregnancy rates, with women in the COVID group having lower pregnancy rates if infected in proximity to the transfer (21% vs. 55%; p = 0.006). In a logistic regression model, infection was a significant variable (p = 0.05, OR 0.325, 95% CI 0.106-0.998). Logistic regression applied on the subgroup of women infected in proximity to the transfer further strengthened the univariate results, with COVID-19 remaining a significant parameter (p = 0.005, OR 0.072, 95% CI 0.012-0.450). CONCLUSIONS: In FET cycles of patients with past SARS-CoV-2 infection, in which oocytes were retrieved prior to infection, decreased pregnancy rates were observed, specifically in patients who recovered less than 60 days prior to embryo transfer. Pending further studies, in cases of FET cycles with limited number of embryos, postponing embryo transfer for at least 60 days following recovery from COVID-19 might be considered when feasible.

The Fer tyrosine kinase protects sperm from spontaneous acrosome reaction.

The physiological acrosome reaction occurs after mammalian spermatozoa undergo a process called capacitation in the female reproductive tract. Only acrosome reacted spermatozoon can penetrate the egg zona-pellucida and fertilize the egg. Sperm also contain several mechanisms that protect it from undergoing spontaneous acrosome reaction (sAR), a process that can occur in sperm before reaching proximity to the egg and that abrogates fertilization. We previously showed that calmodulin-kinase II (CaMKII) and phospholipase D (PLD) are involved in preventing sAR through two distinct pathways that enhance F-actin formation during capacitation. Here, we describe a novel additional pathway involving the tyrosine kinase Fer in a mechanism that also prevents sAR by enhancing actin polymerization during sperm capacitation. We further show that protein-kinase A (PKA) and the tyrosine-kinase Src, as well as PLD, direct Fer phosphorylation/activation. Activated Fer inhibits the Ser/Thr phosphatase PP1, thereby leading to CaMKII activation, actin polymerization, and sAR inhibition.

Coronavirus disease 2019 vaccination and infertility treatment outcomes.

OBJECTIVE: To assess the influence of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid vaccine on ovarian response and in vitro fertilization (IVF) treatment outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary university-affiliated medical center and a private medical center. PATIENT(S): The study included a total of 400 patients, 200 vaccinated women and 200 age-matched unvaccinated women, who underwent IVF in January-April 2021. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The mean number of oocytes retrieved and clinical pregnancy rates in vaccinated vs. unvaccinated patients. RESULT(S): A total of 200 patients underwent oocyte retrieval 14-68 days after receiving COVID-19 vaccination. No difference was found in the mean number of oocytes retrieved per cycle (10.63 vs. 10.72) between vaccinated and unvaccinated patients. Among 128 vaccinated and 133 unvaccinated patients who underwent fresh embryos transfers, no difference was demonstrated in the clinical pregnancy rates (32.8% vs. 33.1%), with 42 and 44 clinical pregnancies, respectively. The fertilization rates and mean number of cryopreserved embryos were similar between the 2 groups in freeze-all cycles (55.43% vs. 54.29% and 3.59 vs. 3.28, respectively). Among vaccinated and unvaccinated patients who underwent fresh embryo transfers, no difference was noted in the fertilization rate (64.81% vs. 61.98%) and transferred embryos' quality. Regression models applied demonstrated no effect of the vaccine on oocyte yields and pregnancy rates. CONCLUSION(S): The COVID-19 messenger ribonucleic acid vaccine did not affect the ovarian response or pregnancy rates in IVF treatment. Women should be vaccinated for COVID-19 before attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women.

IVF under COVID-19: treatment outcomes of fresh ART cycles.

STUDY QUESTION: Does prior severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women undergoing fertility treatments affect the outcomes of fresh ART cycles? SUMMARY ANSWER: SARS-CoV-2 infection does not affect fresh ART treatment outcomes, except for a possible long-term negative effect on oocyte yield (>180 days postinfection). WHAT IS KNOWN ALREADY: A single previous study suggested no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study, including all SARS-CoV-2 infected women who underwent fresh ART cycles within a year from infection (the first cycle postinfection), between October 2020 and June 2021, matched to non-diagnosed controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients from two large IVF units in Israel who were infected with SARS-CoV-2 and later underwent fresh ART cycles were matched by age to non-diagnosed, non-vaccinated controls. Demographics, cycle characteristics and cycle outcomes, including oocyte yield, maturation rate, fertilization rate, number of frozen embryos per cycle and clinical pregnancy rates, were compared between groups. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and twenty-one infected patients and 121 controls who underwent fresh ART cycles were included. Oocyte yield (12.50 versus 11.29; P = 0.169) and mature oocyte rate (78% versus 82%; P = 0.144) in all fresh cycles were similar between groups, as were fertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (43% versus 40%; P = 0.737) in fresh cycles with an embryo transfer. In a logistic regression model, SARS-CoV-2 infection more than 180 days prior to retrieval had a negative effect on oocyte yield (P = 0.018, Slope = -4.08, 95% CI -7.41 to -0.75), although the sample size was small. LIMITATIONS, REASONS FOR CAUTION: A retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection does not affect treatment outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos and clinical pregnancy rates, in fresh ART cycles, except for a possible long-term negative effect on oocyte yield when retrieval occurs >180 days post-SARS-CoV-2 infection. Further studies are warranted to support these findings. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: 0010-21-HMC, 0094-21-ASF.

Early-onset preeclampsia - The impact of antiphospholipid antibodies on disease severity.

OBJECTIVES: Antiphospholipid antibodies have been associated with various obstetric complications, including recurrent pregnancy loss, preeclampsia, intrauterine growth restriction, placental insufficiency, and late fetal loss. Despite the amassed body of evidence emphasizing the association between antiphospholipid antibodies and preeclampsia, the severity of preeclampsia with regard to antiphospholipid antibodies status has not been elucidated. This study aimed to evaluate whether early-onset preeclampsia with severe features before 34 weeks' gestation is clinically different when associated with antiphospholipid antibodies. STUDY DESIGN: In this retrospective case-control study, we collected data on pregnancy outcomes of 101 women with singleton pregnancies who delivered prior to 34 weeks of gestation due to preeclampsia with severe features. The antiphospholipid antibodies status of 55 of these women was available for analysis. The study group comprised 20 women with positive antiphospholipid antibodies (positive-aPL group), while the control group comprised 35 women without antiphospholipid antibodies (negative-aPL group). Obstetric and neonatal outcomes, laboratory results and pregnancy complications were extracted from medical records. RESULTS: In the clinical setting of early-onset preeclampsia with severe features necessitating delivery before 34 weeks gestation, positive-aPL women were hospitalized earlier (29, IQR 26.3-32, vs. 32, IQR 28-33 weeks gestation, P = 0.05), gave birth at a significantly earlier gestational age (30, IQR 28.3-32.8 vs. 33, IQR 30-34, P = 0.02) with a lower mean birth-weight (1266.7 ±â€¯579.6 vs. 1567.3 ±â€¯539.7 g, P = 0.058) compared with negative-aPL women. Furthermore, platelet nadir was significantly lower for positive-aPL compared with negative-aPL women (97 ±â€¯49×103/µL vs. 141 ±â€¯61×103/µL, P < 0.001) and maximal serum creatinine was higher (1.0 ±â€¯0.3 mg/dL vs. 0.9 ±â€¯0.1 mg/dL, P = 0.03). Rates of neonatal complications were low and comparable between groups, except for higher rates of retinopathy of prematurity requiring treatment in the study group (30.0% vs. 5.7%, p = 0.02), and there was a trend for higher perinatal mortality among study group infants. CONCLUSIONS: The presence of antiphospholipid antibodies in women with early-onset preeclampsia with severe features is associated with earlier, more severe disease course. Expedited screening for antiphospholipid antibodies in cases of early-onset severe preeclampsia may be considered, along with close monitoring for pregnant women with positive antibodies.

Is endothelial function impaired among women with placenta-mediated fetal growth restriction? Evidence from a prospective cohort study using peripheral artery tonometry.

INTRODUCTION: Women with pregnancies complicated by IUGR are at increased risk for future cardiovascular disease. Nevertheless, it is unknown whether endothelial function of women with pregnancies complicated by IUGR is already impaired during pregnancy. Hence, we evaluated maternal endothelial function in pregnancies complicated by IUGR due to placental dysfunction. METHODS: Prospective cohort study assessing systemic endothelial function of women with singleton pregnancies and estimated fetal weight (EFW) below 10th percentile and abnormal umbilical artery flow (n = 15). Control group included women with singleton pregnancies and normal EFW (n = 22). Endothelial function was assessed using EndoPAT™ device which evaluates the change in peripheral vascular tone in reaction to temporal ischemia, a process called reactive hyperemia. The ratio of the readings before and after ischemia is used to assess endothelial function and called reactive hyperemia index (RHI). Low RHI values indicate endothelial dysfunction. RESULTS: The median gestational age at endoPAT examination was comparable between the IUGR and control groups (32; IQR 31,33; p = 0.18). The median RHI was significantly lower in the IUGR group compared to the control group (1.3 vs 1.5, p = 0.02). Median gestational age at delivery and mean neonatal birth weight were lower in the IUGR group compared to the control group (36.7 (35.6,37.2) vs 37.7 (35.3, 39.3), p = 0.04 and 1647 ± 414 g vs 2785 ± 587 g, p < 0.001). DISCUSSION-: Pregnant women with IUGR due to placental dysfunction are characterized by impaired systemic endothelial function.

Postpartum visits in the gynecological emergency room: How can we improve?

BACKGROUND: The attendance to the gynecological-emergency-room (GER) of women only a few weeks following previous discharge after birth comprises a medical as well as social problem. The objective of the study was to characterize the postpartum women that attended the GER, and depict the leading etiologies and risk-factors that lead them to attend the GER, and to examine correlations between their medical findings at discharge and the reasons for their attendance to the hospital. METHODS: All women that attended the GER between 01/01/2016 and 30/09/2016 during 6 weeks after birth were included. The variables assessed were: medical history, mode of birth, maternal complications of birth, diagnosis at the GER, treatment received and readmission. RESULTS: There were 446 visits of 413 women (5.6% of all deliveries). Most were generally healthy after their first normal vaginal birth with no complications during or following birth. 38.7% had a cesarean birth (p < 0.001). The most common causes of the visits were fever (30.3%), problems in episiotomy or surgical scar (26.6%) and abdominal pain (25.7%). Women with hypertensive disorders during birth had significantly more hypertensive problems in the GER. Diabetic women suffered statistically more from hypertensive disorder in the GER. 33.2% were examined and found healthy. Seventy-two women (1% of all deliveries) were hospitalized, most of them due to infection. Only 7.5% were referred to the GER due to bleeding. CONCLUSIONS: Postpartum women are at risk of morbidities, especially following cesarean sections and in women with hypertensive disorders of during pregnancy. Scheduled visits to high-risk women to attend outpatient clinic sooner are recommended.