Postpartum hemorrhage among twin pregnancies - Medically assisted versus spontaneously conceived.

INTRODUCTION: In singleton pregnancies, an increased risk of Postpartum hemorrhage (PPH) have been linked with assisted reproductive technology (ART) and abnormal placentation. It is unknown wheather such association exists in twin pregnancies conceived by Medically assisted reproduction (MAR). The aim of the current study was to compare maternal blood loss among twin pregnancies conceived by different types of MAR treatments to spontaneously conceived twins and to identify the cycle characteristics if an association exits. METHODS: Retrospective study conducted on data collected between 2011 and 2020. The study cohort included all twin pregnancies conceived by MAR and born at our institution. Controls were spontaneously conceived twins matched for maternal age on a 1:2 (study: controls) ratio. RESULTS: Overall 113 MAR twin births categorized into three groups; 25 ovulation induction, 59 fresh ART, 29 frozen-thawed ART cycles, and 226 controls were included. The incidence of PPH was higher among MAR twin pregnancies (5.3%) compared to the controls (4%). The highest incidence was observed among women in the frozen-thawed group (13.8%) which differed significantly compared with the controls (p = 0.024). A significant difference was also observed in the mean decrease of postpartum hemoglobin levels between these two groups (2.13 g/dL versus 1.3 g/dL respectively, p = 0.002). Blood transfusion was nearly 2.5 times more common in the frozen-thawed group (3.4%) compared to the control group (1.3%). DISCUSSION: The present study demonstrates that frozen embryo transfer (FET) ART-conceived twin pregnancies are associated with a markedly increased rate of PPH compared to spontaneously conceived twins.

Should pregnant women be screened for SARS-CoV-2 infection? A prospective multicenter cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges from asymptomatic to severe infection. We aimed to compare the prevalence of COVID-19 in asymptomatic pregnant versus nonpregnant women in order to establish recommendations for a COVID-19 screening strategy. METHODS: A prospective multicenter cohort study was conducted. Asymptomatic pregnant or nonpregnant women after March 2020 (the time when COVID-19 was first detected in north Israel) were tested for SARS-CoV-2 using nasopharyngeal reverse transcription polymerase chain reaction test, anti-nucleocapsid IgG, and anti-spike IgG. Diagnosis was made if at least one test result was positive. Pregnant women were tested between 34 and 42 weeks, mostly at birth. RESULTS: Among the 297 participating women, 152 were pregnant and 145 were nonpregnant. The prevalence of asymptomatic COVID-19 was similar between the groups (4 [2.6%] and 8 [5.5%], respectively; P = 0.2). All women with COVID-19 delivered healthy appropriate-for-gestational-age babies without malformations, at term. CONCLUSIONS: The rate of asymptomatic COVID-19 in pregnant women is low and comparable to the rate among nonpregnant women. Pregnancy outcomes are favorable. Future screening programs should consider that one of 25 screened asymptomatic women will be positive.

Perimortem and postmortem sperm acquisition: review of clinical data.

PURPOSE: To provide the clinicians with the most comprehensive medical information about sperm acquisition peri/postmortem. METHODS: The review was conducted according to the PRISMA statement. MEDLINE and Cochrane databases were searched up to January 2021. All studies reporting post or perimortem harvesting of sperm with any indication of an outcome, recognition and viability of sperm, and its utilization and treatment outcome were included. Studies that recorded cases but discussed only the ethical or legal issues without any information about the medical details were excluded. RESULTS: Twenty-four studies were included in this review. One hundred forty-eight cases were described; in 113 of them, sperm was retrieved. A variety of techniques for sperm acquisition were used. The data collected are limited and comparing the efficacy of the different approaches is not feasible. The longest time interval described between the death and viable sperm acquisition was 3 days. The sperm quality varies between the studies. One hundred thirty-six mature oocytes were injected with the retrieved sperm; the fertilization rate was 41%. Transfer cycles of 25 embryos and 8 live births are reported in the medical literature. CONCLUSION: The overall low quality and high heterogeneity of the available data impair the ability to draw definitive conclusions. However, it can be stated that sperm acquisition up to at least 3 days postmortem can result in the live birth of healthy offspring. Further studies are needed to clarify the medical questions regarding the best techniques, success rates, and wellbeing of the parties involved.

Progesterone and estrogen levels are associated with live birth rates following artificial cycle frozen embryo transfers.

PURPOSE: Does an association exist between serum progesterone and estradiol levels and live birth rates in artificial cycle frozen embryo transfer (AC-FET)? METHODS: Retrospective cohort study was based on prospectively collected data at a university-affiliated fertility center. Included were all cycles using an artificial endometrial preparation with estradiol hemihydrate (Estrofem, 2 mg/8 h) and vaginal progesterone (Endometrin 100 mg/8 h), autologous oocytes, and cleavage stage embryo transfers. Serum progesterone and estradiol levels were measured 14 days after FET. A total of 921 cycles in 568 patients from to December 2010 to June 2019 were investigated. Live birth was the primary outcome measure. RESULTS: Significant association was found between live birth and progesterone as well as estradiol levels (progesterone 14.65 vs 11.62 ng/ml, p = 0.001; estradiol 355.12 vs 287.67 pg/ml, p = 0.001). A significant difference in live birth rate was found below and above the median progesterone level (10.9 ng/ml, p = 0.007). Lower estradiol level was significantly associated with lower live birth rate (< 188.2 pg/ml 8.3%, > 263.1 pg/ml 16%, p = 0.02). CONCLUSIONS: Serum progesterone and estradiol levels impact live birth rate in AC-FET.

Ideal lag time from ovulation to oocyte aspiration using a GnRH agonist trigger.

BACKGROUND: In ART, oocyte maturation (M2) and ovulation is stimulated by a hormonal trigger. For maturation to occur, sufficient "lag time" must elapse between the trigger and aspiration, ranging from 32 to 38 hours. Premature aspiration can result in poor yields; late aspiration risks spontaneous ovulation. AIM: Our study examines optimal lag time using a GnRH antagonist protocol and GnRH agonist trigger for ICSI. METHODS AND MATERIALS: We analyzed data from 220 women undergoing GnRH antagonist protocol using a GnRH agonist trigger for ICSI at our clinic between 02/2012-03/2018. Patients were divided into 4 groups based on lag time: 34.00-34.99 hours (n = 32), 35.00-35.99 hours (n = 113), 36.00-36.99 hours (n = 57) and 37.00 h or more (n = 18). Analyses were performed with the Kruskal-Wallis test, Chi-Square, and Spearman's rho correlation. RESULTS: A positive correlation was found for the number of M2 oocytes aspirated and lag time (ρ = 0.138, p = 0.04) and for the total number of oocytes aspirated and lag time, (ρ = 0.174, p = 0.01). No correlation was found between the proportion of M2 oocytes aspirated and lag time (p = 0.217). The third group (36 h) had significantly more M2 oocytes aspirated than the second group (35 h) (12.4 ± 7.1 vs 9.4 ± 6.2; p = 0.039). The four groups did not differ for the proportion of mature M2 oocytes (H = 2.453, p = 0.484). The four groups differed in the frequency of live births per fresh embryos transferred (χ2 = 9.364, p = 0.025). CONCLUSION: Our study identified a positive correlation between lag time and both the number of M2 oocytes and the total number of oocytes aspirated-factors which lead to an increased rate of successful pregnancies. Further research is necessary.

Human umbilical cord perivascular cells prevent chemotherapeutic drug-induced male infertility in a mouse model.

OBJECTIVE: To study whether intratesticular (IT) administration of 2 sources of human umbilical cord perivascular cells (HUCPVC), rich and potent sources of mesenchymal stromal cells (MSC), before chemotherapy can prevent infertility in a mouse model. DESIGN: Two control groups of CD1 male mice without busulfan (BUS) administration (untreated and IT media injection groups) were included. Experimental groups included IT administration of media, first trimester (FTM) HUCPVCs or term HUCPVCs (n = 5 each) injected 3 days before BUS treatment (20 mg/kg). All groups were included in a mating time course study over 6 months. SETTING: Preclinical study in a fertility center research laboratory. PATIENTS: Not applicable. INTERVENTION: IT delivery of FTM or term HUCPVC before BUS treatment. MAIN OUTCOME MEASURES: Pregnancies, litter sizes, and gross morphology of offspring were monitored. Caudal epididymal sperm concentration, motility, and progressive motility were assessed by computer-assisted sperm analysis. Spermatogenesis was also assessed histologically in testicular tissue sections. RESULTS: FTM and term HUCPVC displayed an MSC-associated immunophenotype and expressed transcripts encoding paracrine factors known to regulate the testicular cell niche. IT administration of FTM and term HUCPVC before chemotherapy promoted the recovery of spermatogenesis and fertility compared with BUS-treated animals that received a media injection. Although the total number of pups sired over 6 months by males treated with FTM or term HUCPVC was reduced compared with untreated or media-injected controls, litter size and sperm parameters in fertile animals did not differ between control and cell-treated groups. CONCLUSION: HUCPVC represent a promising source of MSC-based therapy to prevent gonadotoxic chemotherapeutic drug-induced infertility.

Fertility preservation for transgender adolescents and young adults: a systematic review.

BACKGROUND: Many transgender individuals choose to undergo gender-affirming hormone treatment (GAHT) and/or sex reassignment surgery (SRS) to alleviate the distress that is associated with gender dysphoria. Although these treatment options often succeed in alleviating such symptoms, they can also negatively impact future reproductive potential. OBJECTIVE AND RATIONALE: The purpose of this systematic review was to synthesize the available psychosocial and medical literature on fertility preservation (FP) for transgender adolescents and young adults (TAYAs), to identify gaps in the current research and provide suggestions for future research directions. SEARCH METHODS: A systematic review of English peer-reviewed papers published from 2001 onwards, using the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines, was conducted. Four journal databases (Ovid MEDLINE, PubMed Medline, Ovid Embase and Ovid PsychINFO) were used to identify all relevant studies exploring psychosocial or medical aspects of FP in TAYAs. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Bibliographies of the selected articles were also hand searched and cross-checked to ensure comprehensive coverage. All selected papers were independently reviewed by the co-authors. Characteristics of the studies, objectives and key findings were extracted, and a systematic review was conducted. OUTCOMES: Included in the study were 19 psychosocial-based research papers and 21 medical-based research papers that explore fertility-related aspects specific for this population. Key psychosocial themes included the desire to have children for TAYAs; FP discussions, counselling and referrals provided by healthcare providers (HCPs); FP utilization; the attitudes, knowledge and beliefs of TAYAs, HCPs and the parents/guardians of TAYAs; and barriers to accessing FP. Key medical themes included fertility-related effects of GAHT, FP options and outcomes. From a synthesis of the literature, we conclude that there are many barriers preventing TAYAs from pursuing FP, including a lack of awareness of FP options, high costs, invasiveness of the available procedures and the potential psychological impact of the FP process. The available medical data on the reproductive effects of GAHT are diverse, and while detrimental effects are anticipated, the extent to which these effects are reversible is unknown. WIDER IMPLICATIONS: FP counselling should begin as early as possible as a standard of care before GAHT to allow time for informed decisions. The current lack of high-quality medical data specific to FP counselling practice for this population means there is a reliance on expert opinion and extrapolation from studies in the cisgender population. Future research should include large-scale cohort studies (preferably multi-centered), longitudinal studies of TAYAs across the FP process, qualitative studies of the parents/guardians of TAYAs and studies evaluating the effectiveness of different strategies to improve the attitudes, knowledge and beliefs of HCPs.

Gonadotropin Releasing Hormone Agonist Final Oocyte Maturation and Human Chorionic Gonadotropin as Exclusive Luteal Support in Normal Responders.

BACKGROUND/AIMS: Gonadotropin releasing hormone (GnRH) agonist triggering results in an endogenous gonadotropin flare. Although it effectively stimulates ovulation, GnRH agonist triggers results in an early luteolysis and requires modification of the luteal support. The current study aims to evaluate GnRH agonist triggering with exclusive human chorionic gonadotropin (hCG) luteal support. METHODS: In this prospective observational study, 56 normogonadotropic-assisted reproductive technology patients, stimulated using a GnRH-antagonist protocol, were studied. Final oocyte maturation was achieved with 0.2 mg triptorelin acetate followed by progesterone free luteal support with human choriogonadotropin (1,500 IU * 2). A control group was selected from a pool of 1,023 normogonadotropic patients who received Choriogonadotropin alfa for final oocyte maturation and progesterone suppositories for luteal support. RESULTS: No significant difference was found for the number of oocytes, oocyte maturation rate, fertilization and implantation rate, clinical pregnancy rate (25 vs. 26.7%) and live birth rate (25 vs. 21.4%). Progesterone levels in conception cycles were significantly higher in the study group than corresponding levels in the control group. CONCLUSION: GnRH agonist triggering with exclusive hCG support may be a valid alternative to hCG triggering with progesterone support. This protocol combines the potential advantages of a physiological trigger with a simple, patient-friendly, luteal support.

Increased coagulation index as measured by Thromboelastography during ovarian stimulation for in vitro fertilization: Influence of the final oocyte maturation triggering agent.

OBJECTIVE: Thromboelastography (TEG) is a viscoelastic test of hemostasis which allows measurement of the processes of clot initiation, propagation, stabilization, and dissolution in real time. In this study we aimed to evaluate the alterations in coagulation as measured by TEG during In Vitro Fertilization (IVF) stimulation cycles and to investigate whether final oocyte maturation with recombinant hCG (rhCG) versus GnRH agonist results in a different coagulation state. STUDY DESIGN: This is a prospective observational study which included fifty-three normogonadotrophic women. All the patients received an antagonist IVF treatment protocol. Final oocyte maturation was triggered with either rhCG (n = 25) or GnRH agonist (n = 26). Two patients did not complete the study due to poor response. Venous blood was drawn in the early and late follicular phase and on the day of ovum pickup. The TEG parameters assessed were R (time to first clot formation), K (time until the clot reaches a fixed strength), alpha angle (the rate of clot formation), MA (reflects maximum strength of the platelet-fibrin clot), LY30 (percent of clot lysis at 30 min after MA is reached) and the CI (the overall coagulability). RESULTS: The overall coagulation index of the entire study population was significantly increased on the day of ovum pickup as compared to the early follicular phase. This increase in the coagulation index was also significant in a subanalysis of patients triggered with rhCG. Contrarily, there was no significant increase in the coagulation index in the subgroup of patients triggered with GnRH agonist. CONCLUSION: Our results demonstrate a procoagulable state in patients after ovulation induction. Final triggering with GnRH agonist rather than rhCG, might lower this hypercoagulability pattern.

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules.

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

Nifedipine compared with atosiban for treating preterm labor: a randomized controlled trial.

OBJECTIVE: To compare the tocolytic efficacy and tolerability of nifedipine with that of atosiban among pregnant women with preterm labor. METHODS: Pregnant women admitted with preterm labor and intact membranes between 24 and 33 weeks 6 days of gestation, between January 2008 and December 2011, were randomly assigned to either atosiban or nifedipine treatment. Assigned treatment was planned for up to 48 hours. If progress was determined after 1 hour or more, a crossover of the study drugs was performed. The primary outcome was to estimate the tocolytic efficacy and tolerability profile that was assessed in terms of the proportion of women who were not delivered and did not require an alternate tocolytic agent within 48 hours. Secondary outcomes were gestational age at delivery and neonatal morbidity. RESULTS: Seventy-five women in the nifedipine group and 70 in the atosiban group were included and analyzed. Baseline demographic and obstetric characteristics were comparable. Forty-eight (68.6%) women allocated to atosiban and 39 (52%) to nifedipine did not deliver and did not require an alternate agent at 48 hours respectively (P=.03). At 7 days from enrollment, 55 (78.6%) women allocated to atosiban and 67 (89.3%) to nifedipine remained undelivered with or without a rescue agent (P=.02). Mean gestational age at delivery was 35.2 (±3.0) and 36.4 (±2.8) weeks among the atosiban and nifedipine groups, respectively (P=.01). Mean birth weight and neonatal morbidity were comparable. CONCLUSIONS: Atosiban has fewer failures within 48 hours. Nifedipine may be associated with a longer postponement of delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00599898.

The association between maternal characteristics and different types and levels of discordance in triplet pregnancies.

OBJECTIVE: This study evaluated the association of maternal factors known to influence outcomes of triplets, different discordance levels (-25, 25.1-35, and )35%), and three types (according to the birth weight of the middle-sized triplet) of birth weight discordance in triplets. METHODS: We used data collected by the Women's Health Division of Matria Healthcare, Inc. (Marietta, GA). We analyzed a cohort of 2706 triplet sets, to calculate the frequencies of different levels and types of birth weight discordance by maternal age, parity, weight, height, body mass index and weight gain at 24 weeks of gestation. RESULTS: We found a positive association between maternal parity and birth weight discordance level but no clear association between the other maternal factors and the level of discordance as well as the type of discordance. However, a trend was seen whereby overweight women had a trend towards the low-skew (a set comprising one large and two small triplets) type of birth weight discordance and an opposite trend in underweight women. CONCLUSIONS: These results corroborate previous findings that nulliparity is associated with aberrant growth in triplet pregnancies.