Differences In Miscarriages Research Articles

Outcomes of SARS-CoV-2 infection in early pregnancy-A systematic review and meta-analysis.

Available data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes mostly refer to women contracting the infection during advanced pregnancy or close to delivery. There is limited information on the association between SARS-CoV-2 infection in early pregnancy and outcomes thereof. We aimed to systematically review the maternal, fetal and neonatal outcomes following SARS-CoV-2 infection in early pregnancy, defined as <20 weeks of gestation (PROSPERO Registration 2020 CRD42020177673). Searches were carried out in PubMed, Medline, EMBASE, and Scopus databases from January 2020 until April 2023 and the WHO database of publications on coronavirus disease 2019 (COVID-19) from December 2019 to April 2023. Cohort and case-control studies on COVID-19 occurring in early pregnancy that reported data on maternal, fetal, and neonatal outcomes were included. Case reports and studies reporting only exposure to SARS-CoV-2 or not stratifying outcomes based on gestational age were excluded. Data were extracted in duplicate. Meta-analyses were conducted when appropriate, using R meta (R version 4.0.5). A total of 18 studies, 12 retrospective and six prospective, were included in this review, reporting on 10 147 SARS-CoV-2-positive women infected in early pregnancy, 9533 neonates, and 180 882 SARS-CoV-2 negative women. The studies had low to moderate risk of bias according to the Newcastle-Ottawa quality assessment Scale. The studies showed significant clinical and methodological heterogeneity. A meta-analysis could be performed only on the outcome miscarriage rate, with a pooled random effect odds ratio of 1.44 (95% confidence interval 0.96-2.18), showing no statistical difference in miscarriage in SARS-CoV-2-infected women. Individual studies reported increased incidences of stillbirth, low birthweight and preterm birth among neonates born to mothers affected by COVID-19 in early pregnancy; however, these results were not consistent among all studies. In this comprehensive systematic review of available evidence, we identified no statistically significant adverse association between SARS-CoV-2 infection in early pregnancy (before 20 weeks of gestation) and fetal, neonatal, or maternal outcomes. However, a 44% increase in miscarriage rate is concerning and further studies of larger sample size are needed to confirm or refute our findings.

P-693 IVF outcome in patients with thyroid disease

Abstract Study question What is the thyroid disease rate in IVF patients and how does it affect their IVF outcome? Summary answer The thyroid disease rate was 19,5%, mostly of inflammatory origin. IVF outcome in these patients was similar to controls, but coexisting endometriosis rate was higher. What is known already Thyroid disease is the most common endocrine disorder in females of reproductive age. It is estimated that 20% of infertile females has history of thyroid disease. Thyroid hormones importantly impact fertility, acting directly on oocytes, sperm and embryo during fertilization, implantation and placentation, regulating estrogen and androgen metabolism as well as the menstrual cycle. The most common causes of thyroid disfunction are autoimmune disorders. The prevalence of thyroid autoimmunity among women undergoing IVF treatment is higher compared to the general population. Women with thyroid autoimmunity have higher risk of miscarriage, preterm birth and it may impact the IVF-ET outcome. Study design, size, duration It was a single center trial at the Division of Obstetrics and Gynecology, Department of Human Reproduction in the University Medical Centre of Ljubljana, Slovenia. The study included women undergoing their first IVF treatment in a one-year period. Participants/materials, setting, methods A total of 226 women undergoing their first IVF treatment were included. In the first part of our study, Patient characteristics and IVF outcome according to different TSH serum levels (&amp;lt; 0,59 mE/L, 0,59 - 2,5 mE/L, 2,5 - 4,23 mE/L ter &amp;gt; 4,23 mE/L) were analysed. In the second part of the study, we compared patient characteristics and IVF outcome in patients with and without thyroid disease. Main results and the role of chance The average age was 33 ± 4,7 years, the average BMI was 24±4,9 kg/m2. Three percent of women had TSH levels &amp;lt;0,59 mE/L, 74% had TSH levels 0,59-2,5 mE/L,18% had TSH levels 2,5-4,23 mE/L and 6% had TSH levels &amp;gt;4,23 mE/L. The obesity rate (BMI&amp;gt;30 kg/m2) was significantly different in all four groups of patients with the highest rate in the group of TSH 2,5-4,23 mE/L. Thyroid disease was found in 19,5% of patients (thyroid autoimmunity 18%, Hashimoto's thyroiditis 7,5% of patients). The thyroid disease rate was significantly different in all four groups with highest rate in group having TSH &amp;gt;4,23 mE/L and the lowest rate in group having TSH 0,59-2,5 mE/L. Endometriosis was diagnosed in 22% of patients with highest rate in patients having highest TSH levels. There was no correlation between patient characteristics and reproductive history (age, irregular menstrual cycle, dysmenorrhea, pregnancy, spontaneous abortion, recurrent abortion, FSH and LH serum levels) and TSH levels or preexisting thyroid disease. There were no significant differences in the IVF outcome (numbers of retrieved oocytes, immature oocytes and number of embryos) according to TSH levels or preexisting thyroid disease. Thyroid disease rate was significantly higher in patients with endometriosis. Limitations, reasons for caution Our study limitation is a smaller sample size that may affect our results, specifically the differences in the IVF outcome. There was no statistical difference in miscarriage and recurrent miscarriage rate in women with thyroid disease and women with normal thyroid function. Wider implications of the findings Our study gives an insight to the characteristics of women with thyroid disease undergoing IVF treatment in our facility, although the differences were statistically insignificant. As a secondary outcome we discovered a statistically significant correlation of endometriosis and inflammatory thyroid disease, which is rarely mentioed in the literature. Trial registration number not applicable

P-150 clinical pregnancy rates of oocyte donor cycles are similar when universal media and/or oocyte-specific media are used for oocyte vitrification and warming

Abstract Study question Did the use of universal vitrification/warming media have an impact on the clinical pregnancy rates in oocyte donation cycles compared with oocyte-specific vitrification/warming media? Summary answer Using universal media for oocyte vitrification and warming yields similar clinical pregnancy rates but higher oocyte survival rates than oocyte-specific media. What is known already Vitrification is now the gold standard for oocyte and embryo cryopreservation. Several commercial kits are available, some are designed for specific cell types (e.g., oocytes, zygotes, cleavage-stage embryos or blastocysts) and others are suitable for several stages, therefore termed “universal”. While the composition and the exposition protocol of stage specific media are optimized for specific cell types, “universal” media display a single composition, therefore exposition protocols need to be adapted to each specific developmental stage to ensure optimal cell survival rates. The potential use of the universal media allows to optimize the management of media in ART laboratories. Study design, size, duration This is a retrospective monocentric study. We compared the results obtained in our center for oocyte vitrification in donor cycles with the successive use of oocyte-specific vitrification/warming media (RapidVit/Warm™ Oocyte, Vitrolife) and afterwards universal vitrification/warming media (RapidVit/Warm™ Omni, Vitrolife). We analyzed 111 oocyte recipient ICSI cycles performed between March 2016 and July 2020 (86 recipient couples) and their 81 corresponding oocyte donation cycles (79 donors) with these media. Participants/materials, setting, methods Oocyte recipient ICSI cycles were divided in three groups depending on the combination of vitrification and warming media used for the oocyte vitrification and warming procedures: “specific/specific” (S/S), “specific/universal” (S/U) and “universal/universal” (U/U). The primary outcome was the clinical pregnancy rate per embryo transfer. Secondary outcomes were the oocyte survival rates, fertilization rates, cleavage and blastocyst rates, live birth and miscarriage rates. Main results and the role of chance The age of the donors (31.7+/-3.6 yo) and the recipients (35.1+/-4.5) was similar for the three groups (p &amp;gt; 0.05). Total FSH dose was similar for the 3 groups (1814.2+/-505UI) (p &amp;gt; 0.05) Clinical pregnancy rates were similar when universal vitrification/warming media were used (25.6% for S/U; 25.8% for U/U) compared with oocyte-specific vitrification/warming media (12.2% for S/S, p = 0.25). We observed higher oocyte survival rates when universal media were used (93.7% for U/U, 85.5% for S/U) compared with the use of the oocyte-specific media (75.6% for S/S, p &amp;lt; 0.0001). Fertilization (74.9% for U/U; 68% for S/U; 68.1% for S/S), cleavage (97.9% for U/U; 94.6% for S/U; 89.3% for S/S), and blastulation rates (46.6% for U/U; 50.3% for S/U; 41.7% for S/S) were not different between the three groups (p &amp;gt; 0.05). There was no difference in miscarriage (6.5% for U/U; 10.2% for S/U; 4.9% for S/S) and live birth rates (19.4% for U/U; 15.4% for S/U; 7.3% for S/S) between the 3 groups (p &amp;gt; 0.05). Limitations, reasons for caution The preliminary results of this retrospective study need to be confirmed by a larger prospective study. Wider implications of the findings The use of vitrification/warming universal media, which improves the management of media used for vitrification of oocytes and embryos in ART laboratory, allows to obtain similar clinical pregnancy rates for oocyte recipient donors. Trial registration number not applicable

Can Time-Lapse Incubation and Monitoring Be Beneficial to Assisted Reproduction Technology Outcomes? A Randomized Controlled Trial Using Day 3 Double Embryo Transfer.

Objective: To determine if the application of time-lapse incubation and monitoring can be beneficial to clinical outcomes in assisted reproductive technology.Methods: A total of 600 patients were equally randomized to three groups, namely, conventional embryo culture and standard morphological selection (CM group), time-lapse culture and standard morphological selection (TLM group), and time-lapse culture and morphokinetic selection (TLA group). Notably, 424 undergoing fresh autologous in vitro fertilization cycles were analyzed, 132 patients in the CM group, 158 in the TLM group, and 134 in the TLA group. Main outcomes included clinical outcomes, embryo development rates, and perinatal outcomes.Results: Clinical pregnancy rates in the time-lapse groups were significantly higher than in the CM group (CM 65.2% vs. TLM 77.2% vs. TLA 81.3%). Implantation rates and live birth rates were significantly higher for the TLA group (59.7 and 70.9%) compared with the CM group (47.7 and 56.1%) but not compared with the TLM group (55.4 and 67.1%). There was no statistical difference in miscarriage and ectopic pregnancy rates among the three groups. Overall, birth weight was significantly higher in the time-lapse groups (CM 2,731.7 ± 644.8 g vs. TLM 3,066.5 ± 595.4 g vs. TLA 2,967.4 ± 590.0 g). The birth height of newborns in the TLM group was significantly longer than that of the CM group and TLA group (CM 48.3± 4.4 cm vs. TLM 49.8± 2.3 cm vs. TLA 48.5± 2.7 cm).Conclusion: Time-lapse incubation and monitoring have a significant benefit on clinical pregnancy rates and on overall birth weights while morphokinetic analysis is not necessary.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02974517].

P–320 Endometrial flushing to improve fertility outcomes: a systematic review and meta-analysis

Abstract Study question Does flushing the endometrial cavity improve fertility outcomes in couples with infertility and what are the preferred flushing mediums? Summary answer Flushing the endometrial cavity appears to improve live birth rate, implantation rate and clinical pregnancy rate. There was no difference in miscarriage or complication rate. What is known already Live birth rate was improved in cleavage-stage transfer when the uterus was flushed with human chorionic gonadotropin (hCG) at a dose &amp;gt;500 IU in a Cochrane review (Craciunas L et al 2018). Chemical and clinical pregnancy rates and implantation rate may be improved by endometrial flushing with platelet-rich plasma (PRP) in a meta-analysis by Maleki-Hajiagha A et al 2020. Flushing the cavity with oil-based contrast at hysterosalpingography (HSG) improved pregnancy rates when compared with water-based contrast in a systematic review by Fang F et al 2018. Study design, size, duration Our study was a systematic review and meta-analysis. We searched MEDLINE (1946 to December 2020), Embase (1980 to December 2020), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1961 to 9 December 2020) PsychINFO (1806 to December 2020). We screened the titles of search results to identify studies for inclusion and then screened abstracts and full texts to ensure trials met search criteria. Participants/materials, setting, methods We included in this review all randomised controlled trials (RCTs), quasi-experimental or cohort studies evaluating intrauterine instillation or flushing with any medium, irrespective of timing of intervention and irrespective of language or country of origin. We performed the meta-analyses using a random-effects model and performed subgroup and sensitivity analysis. Two authors independently extracted the data. We calculated the risk ratio or odds ratio with 95% confidence intervals based on intention-to-treat or available data analysis. Main results and the role of chance We included 36 RCTs and 12 non-randomised trials including 12230 participants. The sample size varied from 15 to 1186. We included 11 comparisons. Primary outcomes were healthy baby rate and live birth rate. Healthy baby rate was not reported in any of the trials. Live birth rate favoured oil soluble contrast medium (at HSG) when compared to water based contrast medium (OR 0.64, 95% CI 0.52 to 0.78, 2 RCTs and 1 cohort study, 2050 participants, I2 = 86%) or no intervention (OR 3.53, 95% CI 1.64 to 7.60, 2 RCTs, 192 participants, I2 = 0%). With regards to our secondary outcomes: CSF instillation, HCG instillation, PRP instillation and oil-soluble contrast medium at HSG (over water-soluble contrast medium) were favoured for implantation rate and clinical pregnancy rate. There was no statistically significant difference in miscarriage or complication rate for any of the comparisons. All trials were at an overall high risk of bias when assessed on the following areas: sequence generation, allocation concealment, blinding of participants, personnel, and outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias. Limitations, reasons for caution Only 36 studies included were RCTs. Twelve of the RCTs had post randomisation drop outs. There was a lack of detail on the instillation medium for several of the included studies. There was no placebo used in many of the control groups. All meta-analyses had high levels of heterogeneity. Wider implications of the findings: Our findings are in keeping with the literature suggesting a possible improvement in live birth rate following flushing the endometrium with oil soluble contrast medium when compared with a control group. Mechanistic studies are now required to understand how oil-based medium improves fertility. Trial registration number NA

P–281 Is it worth to go to blastocyst when there are less than 4 embryos on day 3?

Abstract Study question Are pregnancy rates similar with blastocyst transfer compared to D3 transfer for patient with a poor embryo yield. Summary answer In poor prognosis patients, more D3 embryos are needed to result in similar outcome compared to single blastocyst and it increases the multiple pregnancy risk. What is known already Good prognosis patients benefit from a blastocyst transfer rather than cleavage-stage embryo because day 3 morphology has limited predictive value for subsequent developmental. A Cochrane meta-analysis in 2016 found a higher live birth rate per transfer in the blastocyst group compared to cleavage-stage and no difference in miscarriage and multiple pregnancies. However, in unselected patients, studies have yielded conflicting results and especially in poor prognosis patients at risk of transfer cancellation. A threshold of four good embryos on the third day has been previously correlated with blastocyst yield and live birth rate compared with cleavage-stage embryo transfer. Study design, size, duration We analyzed the outcome of 1115 cycles with less than 4 embryos during 2019–2020 and compared the results between two groups of D3 and D5 transfers. Participants/materials, setting, methods Amongst 1115 study cycles, in 691 cycles a D3 transfer was performed and in 424 cycles a D5 transfer was performed. We compared transfer cancellation rates, mean number of transferred embryos and ongoing pregnancy rates between the two groups and also in subgroups with female age &amp;lt;37 and female age &amp;gt;37. The statistical analyses were done by Chi square and t-test for paired samples. Main results and the role of chance In the overall study population, the mean female age was 36.3 ± 4.3 years, the mean number of obtained embryos was 2.4 ± 1.0, the mean number of transferred embryos was 1.4 ± 0.8. 17.2% of the cycles resulted in transfer cancellation (6.2% in D3 transfer group and 35.0% in D5 transfer group). After D3 transfer the ongoing pregnancy rate (OPR) per transfer was 21.5% compared to 39.7% in D5 transfers (p &amp;lt; 0.05). A similar pattern was observed in subgroups of age &amp;lt;37 years and &amp;gt;37 years with OPR per transfer significantly higher when D5 transfer was performed. Notably more embryos were transferred on D3 compared to D5 (mean number 1.4 for D3 and 1 for D5). Nonetheless, OPR were similar per cycle in both groups and subgroups of different ages. Limitations, reasons for caution A prospective randomized controlled trial is needed to confirm these results that are consistent with previously reports on retrospective and observational studies. Wider implications of the findings: In poor prognosis patients with low embryo yield, D3 and D5 transfers result in similar OPR per cycle. Transferring at blastocyst stage is not inferior to D3, despite the high cancellation rate, and appears safer permitting a single embryo transfer to avoid multiple pregnancy. Trial registration number Not applicable

Expectant management versus multifetal pregnancy reduction in dichorionic triamniotic (DCTA) triplets: Single centre experience

ObjectivesIn trichorionic triplet pregnancies, multifetal pregnancy reduction (MFPR) reduces the risk of preterm birth, neonatal morbidity and mortality without increasing miscarriage. A similar benefit has been suggested in dichorionic triamniotic (DCTA) pregnancy, but multiple methods are currently used. This study investigates if the method of reduction used in DCTA triplet pregnancy influences the evidence of benefit from MFPR. MethodsThis is a retrospective cohort study of DCTA pregnancies between 2010 and 2019 who attended a single UK fetal medicine tertiary referral center. Cohorts were defined based on MFPR decision and method. The primary outcome was offspring survival until neonatal discharge. The secondary outcomes included miscarriage, preterm birth, livebirth, rates of small for gestational age (SGA) neonates, ans maternal morbidity. To evaluate the differences in neonatal survival until discharge we used Cox proportional regression to calculate hazard rates (HR) and 95% confidence intervals (CI). Differences in secondary outcomes were compared using univariate analysis. ResultsThe study reports the outcomes for 83 DCTA pregnancies. MFPR to DCDA twins was chosen in 19 pregnancies (14 radiofrequency ablation, RFA; 5 intrafetal laser, IFL); in 9 pregnancies selective reduction to a singleton was performed by KCl injection. The rate of pregnancies in with ≥ 1 fetus born alive was not different between groups (p = 0.90). However, the number of expected neonates alive at discharge from hospital was highest in the RFA group (89%, HR 0.28, 95% CI 0.21–0.87, p = 0.02). Rates of premature delivery before 32 weeks (p = 0.02), low birth weight (p < 0.001) and birthweight < 10th percentile (p = 0.01) were all elevated in the expectant management group, compared to women who opted for reduction. There was no difference in miscarriage between groups. ConclusionsOur study suggests that MFPR by RFA, an established and widely available procedure, is of benefit in promoting neonatal survival until discharge in DCTA triplets.

Antioxidants for female subfertility.

Antioxidants for female subfertility.

Obstetrical outcomes of embryo reduction and fetal reduction compared to non-reduced twin pregnancies

To prevent perinatal morbidity and mortality of high-order multiple pregnancy (HOMP), multifetal pregnancy reduction (MPR) is offered to some patients. In this study, we investigated whether twin pregnancies derived from MPRs carry a higher adverse obstetrical outcome compared to non-reduced control group of twins. We retrospectively analyzed the data from HOMPs on which transvaginal ER (n = 153) at a mean gestational age of 7.6weeks or transabdominal FR (n = 59) at a mean gestational age of 12.4weeks was performed between December 2006 and January 2018. The risk of each procedure was evaluated by comparing obstetrical outcome with that of a control population of 157 non-reduced twins conceived by infertility treatment. The mean gestational ages at delivery were 35.2weeks in the ER group, 35.7weeks in the FR group, and 34.1weeks in the control group (P = NS). Compared with those in the control group, the ER group had higher miscarriage (1.3% vs. 6.5%; P = 0.047; OR 0.21; 95% CI 0.45-0.898) and higher overall fetal loss (3.8% vs. 14.4%; P = 0.003; OR 0.24; 95% CI 0.09-0.60) rates. Differently compared with those in the control group, the FR group had no statistical difference in miscarriage (2.5% vs. 1.7%; P=NS) and overall fetal loss (3.8% vs. 6.8%; P=NS) rates. Compared with the control group, ER in twins had a higher miscarriage and fetal loss rate, whereas FR in twins was similar to the control group. So, the FR procedure is overall a better and safer approach of MPR in reducing morbidity and mortality in HOMPs.

Association of sperm source with miscarriage and take-home baby after ICSI in cryptozoospermia: a meta-analysis of testicular and ejaculated sperm.

Miscarriage and take-home baby are the most important issues to patients with cryptozoospermia in receiving intracytoplasmic sperm injection (ICSI). The ICSI usually use ejaculated or testicular sperm. Unfortunately, no synthesized evidence reported miscarriage and take-home baby rate between the two sperm sources. This study aimed to compare the miscarriage and take-home baby rate of ICSI using testicular and ejaculated sperm in patient with cryptozoospermia. We conducted meta-analyses that were based on data from Cochrane library, Ovid, PubMed, ScienceDirect, Scopus, and Web of Science. The pooled analyses used risk ratio (RR) in random-effects model. Sensitivity analyses by subgrouping were completed to explore the associations between mean age and outcome. This study identified 331 potential citations and included four cohort studies for qualitative and quantitative synthesis. The four studies involved 331 patients with 479 ICSI cycles. The results showed no significant difference in miscarriage between testicular sperm group and ejaculated sperm group (RR=1.06, 95% CI 0.48-2.35, p=0.88). Yet, take-home babies per embryo transfer in testicular sperm group (53/226, 23.45%) was more than ejaculated sperm group (59/429, 13.75%) (RR=1.72, 95% CI 1.21-2.44, p=0.002). Similar results can be found in take-home babies per ICSI cycle (RR=1.77, 95% CI 1.28-2.44, p=0.0005), especially in younger couple (RR=1.93, 95% CI 1.11-3.34, p=0.02). No small study bias was detected in the analyses. This study found that testicular sperm has more advantage for ICSI in patients with cryptozoospermia, especially in younger couple. These findings may help guide us when deciding the optimal method of sperm harvest for men with cryptozoospermia. Comparing to ejaculated sperm, testicular sperm showed benefits for take-home baby rate, but not for miscarriage in patients with cryptozoospermia.

Thyroid autoimmunity and intracytoplasmic sperm injection outcome: a systematic review and meta-analysis.

Since 2010, three meta-analyses have been published on the impact of thyroid autoimmunity (TAI) on pregnancy outcomes in infertile women treated with assisted reproductive technology (ART). The initially observed high risk of miscarriage became very low in the most recent meta-analysis published in 2016. To investigate whether the lower risk of miscarriage in the latest meta-analysis was associated with the increased use of intracytoplasmic sperm injection (ICSI) in recent studies. MEDLINE was searched from January, 1990, to May, 2017. Data from case-control and cohort studies, on ART (IVF/ICSI) pregnancy outcomes in women with and without TAI. Only studies were included in which women were treated with ICSI. Four studies were retained including 1855 ICSI cycles (290 with and 1565 without TAI). In women with a clinical pregnancy (114 ICSI cycles with TAI and 651 without), there was no difference in miscarriage or live birth rates: respective combined OR 0.95 (95% CI, 0.48 to 1.87) and 1.12 (95% CI, 0.62 to 2.03). There was no difference in age in women with and without TAI: combined mean difference of 0.13 years (95% CI, -0.51 to 0.76), but serum TSH was higher in women with TAI: combined mean difference of 0.20 mIU/L (95% CI, 0.07 to 0.33). Infertile women with TAI treated with ICSI had no increased risk of a first trimester miscarriage compared with women without TAI.

Effects of embryo transfer quality on pregnancy and live birth delivery rates

To analyze the effects of embryo transfer (ET) quality on clinical pregnancy (CPR) and live birth delivery rates (LBDR). In a retrospective study at a single, private infertility center between November 2005 and December 2009 one thousand fifty-five day-3 and day-5 ETs following IVF/ICSI/IMSI were evaluated. We analyzed the impact of an atraumatic ET with a soft catheter (ET 1), after external guidance (ET 2), after probing of the cervix with a stylet (ET 3), or after grasping the portio vaginalis with a tenaculum (ET 4) on CPR and LBDR. The use of external guidance showed a significantly reduced LBDR as compared to an atraumatic ET (26.0% vs. 32.5%). The lowest CPR and LBDR were found in ET 4. The application of stylets in cases of difficult ETs was superior to the use of external guidance. No differences in miscarriages between ET 1-4 were noted. Besides embryo culture and patient history, the quality of an ET might also have an important impact on pregnancy outcome. Techniques to ensure an atraumatic ET, such as mechanic uterine cavity length measurements, before starting treatment might help identify patients at risk for a difficult ET and lead to modified treatments, such as the primary use of a stylet. Limitation of study: retrospective analysis.