Recurrent Implantation Failure—Is It the Egg or the Chicken?

Recurrent implantation failure (RIF) is an undefined, quite often, clinical phenomenon that can result from the repeated failure of embryo transfers to obtain a viable pregnancy. Careful clinical evaluation prior to assisted reproduction can uncover various treatable causes, including endocrine dysfunction, fibroid(s), polyp(s), adhesions, uterine malformations. Despite the fact that it is often encountered and has a critical role in Assisted Reproductive Technique (ART) and human reproduction, RIF’s do not yet have an agreed-on definition, and its etiologic factors have not been entirely determined. ART is a complex treatment with a variable percentage of success among patients and care providers. ART depends on several factors that are not always known and probably not always the same. When confronted with repeated ART failure, medical care providers should try to determine whether the cause is an embryo or endometrium related. One of the most common causes of pregnancy failure is aneuploidy. Therefore, it is likely that this represents a common cause of RIF. Other RIF potential causes include immune and endometrial factors; however, with a very poorly defined role. Recent data indicate that the possible endometrial causes of RIF are very rare, thereby throwing into doubt all endometrial receptivity assays. All recent reports indicate that the true origin of RIF is probably due to the “egg”.

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study

Background To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic. Methods and findings We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28). When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected. Conclusions We observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

Takotsubo cardiomyopathy in peripartum period: a case report

Cardiomyopathy is a group of disorders characterised by structural and functional abnormalities in the myocardium in the absence of other cardiac diseases of myocardial abnormality. Its occurrence in pregnancy is uncommon and exact incidence is unknown even though some studies shows that the incidence of peripartum cardiomyopathy is 1 in 1000 to 4000 births. Here we have discussed about a 34 years primigravida with twin pregnancy conceived after 12 years of married life by assisted reproductive technique (ART), admitted with preterm premature rupture of membranes (PPROM) at 28 weeks of gestation who developed a rare condition called Takotsubo cardiomyopathy (TC) in the peripartum period. She was managed in intensive care unit with oxygen supplementation, beta blockers, diuretics and heparin. Patient had an excellent recovery in the early postoperative period.

Effect of recombinant follicular stimulating hormone and human menopausal gonadotrophins on the oocytes number in patients undergoing assisted reproductive technique

<p><strong>Background &amp; Objective:</strong> The data regarding the effectiveness of various protocols used for controlled ovarian stimulation (COS) in assisted reproductive techniques (ART) in our own population is scant. This study compares recombinant follicular stimulating hormone (rFSH) and human menopausal gonadotrophins (HMG) in terms of follicular numbers and oocytes retrieved in Pakistani women undergoing ART.</p> <p><strong>Methods</strong>: A total of 300 patients were selected out of 1,950 patients who visited the hospital for in vitro fertilization/intra cytoplasmic sperm insemination (IVF/ICSI) from June 2018 to December 2020. These patients were further divided into two categories: first category (1) was given long protocol and the second category (2) was given short antagonist protocol. Each category was further sub-divided into two groups; group A who received HMG, and group B who received rFSH for COS.</p> <p><strong>Results: </strong>There was a significantly higher number of follicles and oocytes retrieved in category 1, with rFSH (20.01 &plusmn; 4.91, 15.19 &plusmn; 9.18) versus. HMG (16.07 &plusmn; 5.67, 11.10 &plusmn; 5.07) with a p-value (0.00, 0.004). On the other hand, in category 2, the number of follicles was insignificant (p-value = 0.319) in both groups. Contrary to that the number of oocytes retrieved was significantly higher with a p-value of &le; 0.05 in both groups.</p> <p><strong>Conclusion:</strong> In COS in ART, long protocol with rFSH has much better results both in terms of follicular numbers and retrieved oocytes. While for the short protocol with the antagonist, rFSH has been demonstrated to be superior to HMG but that is limited to the number of oocytes.</p>

Study protocol: a multi-center, double-blind, randomized, 6-month, placebo-controlled trial to investigate the effect of supplementing hormone therapy FET cycles with Gushen’antai pills on the outcomes of in vitro fertilization

Background Infertility is a widespread global challenge. Currently, the most effective treatment strategy for infertility is in vitro fertilization (IVF), which is an assisted reproductive technique (ART). The use of IVF for assisted pregnancy dates back to the last 41 years when the first IVF baby was born. During IVF, many oocytes are obtained in an IVF cycle, and more than one embryo is formed. Subsequently, frozen-thawed embryo transfer (FET) is increasingly being used in IVF cycles for women in whom a fresh embryo transfer fails to result in a pregnancy, or in those who return for a second baby. However, the pregnancy success rates following FET treatment cycles are reportedly lower than in fresh embryo transfers. Therefore, recent related studies are increasing determining mechanisms of improving the sustained pregnancy rate of FET and reducing the rate of early abortion. The Gushen’antai pill (GSATP), which contains a mixture of 10 herbs, has been widely used in traditional Chinese medicine (TCM) as a pharmacological option to prevent miscarriage. However, randomized controlled trials (RCT) have never been conducted to provide high-level clinical evidence on the clinical efficacy of GSATP. The objective of this study is to investigate the effect of GSATP of hormone therapy (HT) FET cycles on pregnancy rate. Methods A total of 300 subjects aged between 18 and 40 years which prepared for HT cycle FET will be enrolled in the study. The patients were from five different hospitals, with 60 patients from each hospital. Patients were randomly divided into two groups, and medication was started on the day of endometrial transformation. After FET 28 days, B-ultrasound was done to determine whether to continue the medication. Baseline assessments were carried out before the trial and outcomes were collected 4, 6, 8, 10, and 12 weeks of each gestational cycle. Discussion Differences in ongoing pregnancy rate, clinical pregnancy rate, implantation rate, and threatened abortion rate between the two groups will be statistically analyzed. We can finally have an objective evaluation of the efficacy of the traditional Chinese medicine Gushen’antai pills. Trial registration ChiCTR1900026737. Registered October 20, 2019.

REPRODUCTIVE OUTCOMES AFTER ABDOMINAL MYOMECTOMY

Objective: To determine the frequency of reproductive outcomes after abdominal myomectomy in infertile women. Study Design: Case series. Place and Duration of Study: at Combined Military Hospital, Multan Pakistan, from Sep 2015 to Feb 2017. Methodology: This study included 60 women who underwent myomectomy to retain their capabilities of reproduction. Inclusion criteria were infertile women with uterine fibroids. Routine investigation was done to all patients like ultrasound and hysterosalpingogram before and after the procedure. The procedure of abdominal myomectomy was done under general anesthesia. All fibroids were enucleated and large blood vessels were tied. Vicryl no.1 was used to close the uterine defect. All patients were followed up for 3, 6 and 12 months interval and data was collected for conception, spontaneous conception, and conception with assisted reproductive technique, live birth and miscarriage. Results: In this study mean age was 27.33 ± 4.03 years, mean number of fibroid was 1.366 ± 0.48 and mean size of fibroid was 7.06 ± 1.64 cm. Twenty eight (46.7%) women had conceived after myomectomy, in which 92.9% had spontaneous conception and 7.1% by assisted reproductive technique. Conclusion: Abdominal myomectomy should be the standard treatment of infertile women with uterine fibroids if no other underline cause of infertility. Moreover, this study results also showed that younger patients might be benefited more in term of reproductive outcomes after abdominal myomectomy.

Bilateral tubal incarceration into the broad ligaments caused by pelvic endometriosis: A case report

Introduction: Endometriosis is characterised by the presence of functional endometrial tissue outside the uterus. Salpinges are a common location of endometriotic implants. Endometriosis located into the broad ligament is a rare event. Case description: A 38-year-old infertile woman presented to our attention with moderate left iliac fossa pain after menses and intermenstrual bleeding. Transvaginal ultrasounds and pelvic magnetic resonance evidenced the presence of bilateral haematosalpinges. At the laparoscopic pelvic exploration, fallopian tubes were absent. Opening and dissecting the apical portion of the broad ligaments, we identified bilateral haematosalpinges incarcerated in the homolateral broad ligaments. We performed bilateral salpingectomy. Histological examination confirmed the presence of endometriosis. Conclusion: Care must be taken to the diagnostic assessment, counselling about the surgical programme before the intervention especially in patients during the reproductive period when the possibility of ablative surgery and subsequent need for an assisted reproductive technique exists.

Dietary Fatty Acid Intakes and the Outcomes of Assisted Reproductive Technique in Infertile Women

Background: The purpose of this study was evaluating the relationship between fatty acid (FA) intakes and the Assisted Reproductive Technique (ART) out-comes in infertile women. Methods: In this descriptive longitudinal study, a validated food frequency questionnaire (FFQ) was used to measure dietary intakes among 217 women with primary infertility seeking ART treatments at Isfahan Fertility and Infertili-ty Center, Isfahan, Iran. The average number of total and metaphase II (MII) oocytes, the fertilization rate, the ratio of good and bad quality embryo and bio-chemical and clinical pregnancy were assessed. Analyses were performed using mean, standard deviation, Chi-square test, ANOVA, ANCOVA, logistic regres-sion. Results: A total of 140 women were finally included in the study. There was a positive relationship between the average number of total and MII oocytes and the amount of total fatty acids (TFAs), saturated fatty acids (SFAs), monoun-saturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), linoleic ac-ids, linolenic acids, and oleic acids intakes, while eicosapentaenoic acids (EPAs) and docosahexaenoic acids (DHAs) intakes had an inverse relationship. Consuming more amounts of TFAs, SFAs, PUFAs, MUFAs, linoleic acids, and oleic acids was associated with the lower fertilization rate, whereas the con-sumption of linolenic acids and EPAs increased the fertilization rate. The ratio of good quality embryo was directly affected by the amount of PUFAs intakes. Additionally, there was a negative correlation between the amount of SFAs in-takes and the number of pregnant women. Conclusion: TFAs, SFA, PUFA, and MUFA intakes could have both beneficial and adverse impacts on ART outcomes.

Trend of medically induced monozygotic twin deliveries according to age, parity, and type of assisted reproductive technique during the period 2007–2017 in Lombardy Region, Northern Italy: a population-based study

Purpose The risk of monozygotic (MZT) twinning is increased in pregnancies after assisted reproductive technologies (ART). However, determinants remain poorly understood. To shed more light on this issue, we analyzed the estimated frequency of MZT twins from ART in Lombardy, Northern Italy, during the period 2007–2017. Methods This is a population-based study using regional healthcare databases of Lombardy Region. After having detected the total number of deliveries of sex-concordant and sex-discordant twins from ART, we calculated MZT rate using Weinberg’s method. Standardized ratios (SRs) and corresponding 95% confidence intervals (CI) of MZT deliveries, adjusted for maternal age, were computed according to calendar period, parity, and type of ART. Results On the whole, 19,130 deliveries from ART were identified, of which 3,446 were twins. The estimated rate of MZT births among ART pregnancies was higher but decreased over time (p-value = 0.03); the SRs being 1.33 (95% CI: 1.18–1.51), 0.96 (95% CI: 0.83–1.11), and 0.92 (95% CI: 0.79–1.07) for the periods 2007–2010, 2011–2014, and 2015–2017, respectively. The SRs of MZT among women undergoing first-level techniques, conventional in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were 0.47 (95% CI: 0.38–0.57), 1.02 (95% CI: 0.88–1.17), and 1.43 (95% CI: 1.27–1.61) (p-value < 0.0001). The ratio of MZT births was significantly higher in women younger than 35 years (p-value < 0.0001) and slightly higher among nulliparae (p-value < 0.0001). Conclusion Despite a reduction of MZT rate from ART over the time, the risk remains higher among ART pregnancies rather than natural ones. Younger women and women undergoing ICSI showed the highest risk of all.

P–770 Two in One - Monozygotic splitting and associated perinatal outcomes after oocyte freezing; an exploratory analysis of the UK national database from 1990 to 2016

Study question Is oocyte freezing a risk factor for monozygotic splitting? Summary answer There is a trend towards a higher monozygotic splitting incidence among frozen oocytes, but this did not reach statistical significance. What is known already Laboratory techniques which involve embryo manipulation such as ICSI, assisted hatching, embryo biopsy for pre-implantation genetic testing and extended culture to the blastocyst stage appear to increase the risk of monozygotic splitting. Whilst there is some data that embryo freezing does not appear to increase the risk of monozygotic splitting, there is no comparable analysis on whether oocyte freezing increases the risk of monozygotic splitting. Study design, size, duration This was a retrospective cohort study analysing 988 015 ART (assisted reproductive technique) cycles from the HFEA anonymised database from 1990 to 2016. As frozen oocytes require ICSI, only fresh oocytes with ICSI were taken for comparison and frozen embryo transfers were excluded. Only single embryo transfers were included.[CM1] [MM2] We also noted ages of the female partner at the time of treatment, stage of embryo transfer, and whether pre-implantation genetic testing had been performed. Participants/materials, setting, methods There were 84 085 ICSI cycles with single embryo transfers using fresh oocytes and 596 using frozen oocytes. Monozygotic splitting was defined as the presence of two foetal hearts [CM1] [MM2] on ultrasound. Live birth (LB)was defined as either a singleton or a twin LB resulting from a monozygotically split embryo. Preterm birth (PTB) was defined as birth prior to 37 weeks gestation and early PTB as birth prior to 32 weeks gestation. Main results and the role of chance The frozen oocyte group had fewer women in the under–35 age group (frozen oocytes 16.6% vs fresh oocytes 53.6%, p &lt; 0.0001) and a higher proportion of blastocyst transfers ( frozen oocytes 55.1% vs fresh oocytes 48.8%, p = 0.002) There were only 10 PGT cycles amongst monozygotically split embryos from fresh oocytes in our analysis, and none in the frozen oocyte group. Hence, this was not included as a confounder. There was a non-significant trend toward a higher incidence of monozygotic splitting amongst frozen oocytes (4/596, 2.3%, all monozygotic twins) than amongst fresh oocytes (378/27 019, 1.4%, 372 monozygotic twins and 6 monozygotic triplets); OR 1.688, 95% CI 0.623 to 4.574 and aOR 1.506, 95% CI 0.531 to 4.274 (maternal age and stage of embryo transfer adjusted as confounders). Of the 378 monozygotically split embryos from fresh oocytes, 308 (81.5%) had a LB: of which 47 (15.3%) were singletons and the rest were twins; 241 (78.2%) were PTB and 56 (18.2%) were early PTB. Of the four monozygotic twins from frozen oocytes, all reached a LB; one was a singleton term LB (Birthweight 3–3.5kg) whilst three were twin preterm LBs at 35–36 weeks, with no early PTBs and twin median birthweight 2–2.5 kg. Limitations, reasons for caution Albeit a large national database, this cohort study was restricted due to absence of data on potential confounders such as age at oocyte freezing, method of cryopreservation and length of storage.[CM1] Data was also lacking on amnionicity, obstetric risks including pre-eclampsia, twin-to-twin-transfusion syndrome, intrapartum and late effects. Wider implications of the findings: With rapid rise in egg freezing, our findings would help reassure women that eggs on ice does not predispose to significant risk of two-in-one monozygotic splitting. However, the marginal trend (from 1.4% in fresh to 2.3% in frozen oocytes), does indicate that this subject merits further research. Trial registration number Not applicable. A database based retrospective study