How successful is intrauterine insemination after failed IVF? A study of 551 women.

RESEARCH QUESTION: What is the success rate of intrauterine insemination (IUI) after failing IVF? DESIGN: This retrospective cohort study evaluated the pregnancy outcomes of 551 patients who underwent a total of 992 IUI cycles at an academic fertility centre between October 2008 and April 2018. RESULTS: The study participants (n = 551) had previously failed one to three fresh IVF cycles and any resultant embryo transfers, and subsequently underwent a total of 992 IUI cycles. When comparing demographics, women with ongoing pregnancies, clinical pregnancies and positive pregnancies were significantly younger (P = 0.037, P = 0.025 and P = 0.049, respectively) compared with women who did not conceive. The cumulative ongoing pregnancy rate for all IUI cycles was 7.44% per patient (41 pregnancies in 551 patients), and the ongoing pregnancy rate after the first IUI cycle was 4.72%. In single women who had previously failed six IUI cycles before undergoing IVF cycles with donor sperm, the cumulative ongoing pregnancy rate was 15.8% in donor sperm IUI cycles compared with 5.1% in women who used their partner's sperm for both IVF and IUI cycles, with an adjusted odds ratio of 6.1. Patient age, number of previous pregnancies, daily gonadotrophin dose for IVF, number of mature follicles at trigger, and number of failed IVF cycles failed to predict pregnancy outcomes. CONCLUSION: Ongoing pregnancy following IUI after failed IVF occurs at a rate of approximately 5% per cycle, and this rate is higher if donor sperm is used for both IVF and IUI cycles. This can be considered with proper counselling in women aged <40 years, and may be discouraged in women aged ≥43 years.

Clinical factors associated with unexpected poor or suboptimal response in Poseidon criteria patients.

RESEARCH QUESTION: What clinical factors are associated with 'unexpected' poor or suboptimal responses to IVF ovarian stimulation per POSEIDON's criteria, and which AMH and AFC threshold values distinguish this population? DESIGN: Tri-centre retrospective cohort study (2015-2017) involving first-time IVF and ICSI cycles with conventional ovarian stimulation (≥150 IU/day of FSH). Eligibility criteria included sufficient ovarian reserve markers according to POSEIDON's classification (AMH ≥1.2 ng/ml; AFC ≥5). Ovarian response categories were poor (<4 oocytes), suboptimal (4-9 oocytes) and normal (≥9 oocytes). Primary outcomes included clinical factors associated with an unexpected poor or suboptimal response to conventional ovarian stimulation using logistic regression analyses, and the threshold values of AMH and AFC predicting increased risk of such responses using ROC curves. RESULTS: A total of 7625 patients met the inclusion criteria: 204 (9.3%) were poor and 1998 (90.7%) were suboptimal responders. Logistic regression identified significant clinical predictors for a poor or suboptimal response, including AFC, AMH, total gonadotrophin dose, gonadotrophin type and trigger type (P ≤ 0.02). The ROC curves indicated that AMH 2.87 ng/ml (AUC 0.740) and AFC 12 (AUC 0.826) were the threshold values predicting a poor or suboptimal response; AMH 2.17 ng/ml (AUC 0.741) and AFC 9 (AUC 0.835) predicted a poor response; and AMH 2.97 ng/ml (AUC 0.722) and AFC 12 (AUC 0.801) predicted a suboptimal response. CONCLUSIONS: The threshold values of AMH and AFC predicting 'unexpected' poor or suboptimal response were higher than expected. These findings have critical implications for tailoring IVF stimulation regimens and dosages.

Comparison of luteal phase and follicular phase in-vitro maturation in women with oocyte maturation abnormalities.

RESEARCH QUESTION: Are there differences in immature oocyte retrieval following luteal phase in-vitro maturation (IVM) compared with follicular phase IVM in women with oocyte maturation abnormalities (OMAs). DESIGN: From January 2019 to May 2023, a retrospective cohort study at a private IVF centre included 36 women with 53 IVM cycles in Group 1 (follicular phase) and 24 women with 32 IVM cycles in Group 2 (luteal phase). Additionally, nine women had both follicular and luteal phase IVM cycles for intracycle variability analysis. RESULTS: There were no differences in oocyte maturation stages between the groups at collection. Group 1 and Group 2 exhibited comparable median metaphase II oocyte rates per patient at 48 h after collection [40.0%, interquartile range (IQR) 0.0-66.7% versus 22.5%, IQR 0.0-52.9%] (P = 0.53). The median fertilization rate in Group 1 (66.7%, IQR 50.0-66.7%) was found to be comparable with that in Group 2 (66.7%, IQR 50.0-66.7%). There were no significant differences in the yielded embryo grades and pregnancy rates between the groups. Comparing follicular and luteal phase IVM within the same menstrual cycle in nine patients, no differences were observed in metaphase II oocyte maturation rates (P > 0.05). CONCLUSIONS: This study found no significant differences in oocyte maturation, fertilization rate, embryo quality or pregnancy outcomes between luteal phase and follicular phase IVM in women with OMAs. These findings suggest that luteal phase IVM can be used similarly to follicular phase IVM, offering a potential avenue to enhance embryo yield for women with OMAs.

Oocyte in-vitro maturation primed with letrozole-HCG versus FSH-HCG in women with oocyte maturation abnormalities: a retrospective study.

RESEARCH QUESTION: Are there differences between in-vitro maturation (IVM) primed with letrozole-human chorionic gonadotrophin (HCG) and IVM primed with FSH-HCG in women with oocyte maturation abnormalities (OMAs), defined as at least two failed IVF cycles where immature oocytes were retrieved? DESIGN: This retrospective study was conducted at a private fertility clinic from January 2009 to April 2023. The final analysis included 75 women in Group 1 (IVM primed with FSH-HCG) and 52 women in Group 2 (IVM primed with letrozole-HCG). RESULTS: A significantly higher median number of oocytes was obtained in Group 1 compared with Group 2 {9 [interquartile range (IQR) 1-5] versus 5 (IQR 1-18); P < 0.001}. However, no differences in oocyte maturation stage at collection were found between the groups (P > 0.05). At the end of IVM, Group 1 had 73/666 mature oocytes and Group 2 had 106/322 mature oocytes, and the median metaphase II oocyte rate per patient was higher in Group 2 [33.3% (IQR 66.7-100.0%) versus 0.0% (IQR 0.0-22.2%); P < 0.001]. Moreover, Group 2 demonstrated a higher median fertilization rate [66.7% (IQR 50.0-100.0%) versus 50.0% (IQR 0.0-66.7%); P = 0.027]. Group 2 had a higher proportion of Grade 2 embryos (58.5% versus 6.3%), and Group 1 had a higher proportion of Grade 3 embryos (93.8% vs 24.4%; P < 0.001). Notably, all pregnancies obtained in the study were in Group 2 (5 versus 0; P = 0.042). CONCLUSIONS: IVM primed with letrozole-HCG in women with prior failed IVF cycles due to OMAs may result in mature oocytes, clinical pregnancies and live births. The effectiveness of letrozole priming for the subtypes of OMAs needs further investigation, with studies including greater numbers of cases.

The association between attention deficit hyperactivity disorder and pregnancy, delivery and neonatal outcomes-an evaluation of a population database.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without. METHODS: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without. RESULTS: Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28-1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13-1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17-1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19-1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17-1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36-3.26, p < 0.001). CONCLUSION: Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.

Pregnancy, delivery and neonatal outcomes in women with gastrointestinal system cancer in pregnancy. An evaluation of a population database.

OBJECTIVES: Gastrointestinal system (GIS) cancer in pregnancy is a rare disease. Our aim was to evaluate the association between this type of cancer and pregnancy, delivery and neonatal outcomes. METHODS: We conducted a retrospective population-based cohort study using the Healthcare Cost and Utilization Project, Nation-wide Inpatient Sample (HCUP-NIS). We included all women who delivered or had a maternal death in the US between 2004 and 2014. We compared women with an ICD-9 diagnosis of GIS cancer to those without. Pregnancy, delivery, and neonatal outcomes were compared between the two groups. RESULTS: A total of 9,096,788 women met inclusion criteria. Amongst them, 194 women (2/100,000) had a diagnosis of GIS cancer during pregnancy. Women with GIS cancer, compared to those without, were more likely to be Caucasian, older than 35 years of age, and to suffer from obesity, chronic hypertension, pregestational diabetes and thyroid disease. The cancer group had a lower rate of spontaneous vaginal delivery (aOR 0.2, 95 % CI 0.13-0.27, p<0.001), and a higher rate of preterm delivery (aOR 1.85, 95 % CI 1.21-2.82, p=0.04), and of maternal complications such as blood transfusion (aOR 24.7, 95 % CI 17.11-35.66, p<0.001), disseminated intravascular coagulation (aOR 14.56, 95 % CI 3.56-59.55, p<0.001), venous thromboembolism (aOR 9.4, 95 % CI 2.3-38.42, p=0.002) and maternal death (aOR 8.02, 95 % CI 2.55-25.34, p<0.001). Neonatal outcomes were comparable between the two groups. CONCLUSIONS: Women with a diagnosis of GIS cancer in pregnancy have a higher incidence of maternal complications including maternal death, without any differences in neonatal outcomes.

The effect of bariatric surgery on polycystic ovary syndrome patients' obstetric and neonatal outcomes: a population-based study.

PURPOSE: To examine the effect of bariatric surgery (BS) on obstetric and neonatal outcomes in patients with polycystic ovary syndrome (PCOS). METHODS: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database, including women who delivered in the third trimester or had a maternal death in the USA (2004-2014). We compared obstetric and neonatal outcomes between groups in three analyses: (1) Primary analysis-women with an ICD-9 PCOS diagnosis who underwent BS compared to pregnant PCOS patients without BS. (2) Sub-group analysis-PCOS women with BS compared to obese PCOS women (body mass index (BMI) ≥ 30 kg/m2) without BS. (3) Women with and without PCOS who underwent BS. RESULT: In the primary analysis, pregnant PCOS women who underwent BS (N = 141), compared to pregnant PCOS women without BS (N = 14,741), were less likely to develop pregnancy-induced hypertension (PIH) (9.2% vs. 16.2%, respectively, aOR 0.39, 95% CI 0.21-0.72) and gestational diabetes mellitus (GDM) (9.9% vs. 18.8, aOR 0.40, 95% CI 0.23-0.70). In the sub-group analysis, PCOS women with BS, compared to obese PCOS women without BS (N = 3231), were less likely to develop gestational hypertension, preeclampsia, and preeclampsia or eclampsia superimposed on hypertension (P < 0.05). Lastly, PCOS patients with BS had a higher cesarean section rate when compared to non-PCOS patients with BS (N = 9197) (61.7% vs. 49.2%, aOR 1.48, 95% CI 1.05-2.09), with otherwise comparable obstetric and neonatal outcomes. CONCLUSIONS: BS in PCOS patients was associated with reduced risks for GDM and PIH when compared to PCOS controls without BS and reduced risk for gestational hypertension, preeclampsia, and preeclampsia or eclampsia superimposed on hypertension when compared to obese PCOS controls without BS. Moreover, BS was associated with reduced inherent pregnancy risks of PCOS, almost equating them to those of non-PCOS counterparts.

Significance of serum AMH and antral follicle count discrepancy for the prediction of ovarian stimulation response in Poseidon criteria patients.

PURPOSE: To determine the risk of not being a poor responder in ovarian stimulation (OS) for in vitro fertilization (IVF) when ovarian reserve markers are discordant-one falling within Poseidon's criteria normal range (e.g., anti-Müllerian hormone (AMH) ≥ 1.2 ng/mL or antral follicle count (AFC) ≥ 5), and the other in the poor ovarian reserve range. METHODS: A tri-center retrospective cohort study (2015-2017) involving women with discordant AMH and AFC values undergoing their first IVF/ICSI cycle using conventional OS (cOS, ≥ 150 IU/day of follicle-stimulating hormone). Discordant serum AMH and AFC values were defined according to Poseidon's criteria (AMH < 1.2 ng/mL and AFC ≥ 5 or AMH ≥ 1.2 ng/mL and AFC < 5). Poor ovarian response (POR) was < 4 retrieved oocytes. Receiver operating characteristic (ROC) curves were used to determine AMH and AFC cut-offs for non-POR. Logistic regression analysis evaluated factors associated with non-POR. RESULTS: Out of 8797 patients who underwent assessment with both AMH and AFC, 1172 (13.3%) exhibited discordant values. Of these, 854 (72.9%) had ≥ 4 oocytes retrieved. Within this group, 726 (85.0%) had "low" AMH values, whereas 128 (15.0%) had "low" AFCs. An AFC of 6 had 77% sensitivity and 52% specificity (AUC = 0.700), while AMH of 1.19 ng/mL had 31% sensitivity and 85% specificity (AUC = 0.492) for non-POR. AFC and the use of recombinant gonadotropins were positive predictors of non-POR. CONCLUSIONS: When serum AMH is < 1.19 ng/mL, but AFC is ≥ 6, there is a moderate likelihood of a non-POR during stimulation. Conversely, if AFC is < 5 but serum AMH is ≥ 1.19 ng/mL, the chances of non-POR are low. Among patients with discordant markers, AFC emerges as the primary predictor of oocyte yield.

Changes in adverse obstetrical and neonatal outcomes over time in American women with polycystic ovary syndrome: an 11-year study of a population database.

PURPOSE: To determine whether the prevalence in American demographic and resultant adverse obstetric outcomes changed in women with polycystic ovary syndrome between the years of 2004-2014 inclusively, based on data derived from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database. METHODS: This is a retrospective population-based study using data derived from the HCUP-NIS database from the years of 2004-2014, inclusively. Within this group, all pregnancies to women with PCOS were identified and separated by year, creating 11 groups. RESULTS: Risk factors including non-Caucasian race, lower socioeconomic status, and rates of obesity and thyroid disease increased over time. The rates of gestational diabetes mellitus demonstrated a slight decrease, (21.3% in 2004 to 18.0% in 2014, P = 0.01). The number of women with preterm premature rupture of membranes decreased from 3.0% in 2004 to 2.0% in 2014 (P = 0.04). Rates of preterm delivery decreased from 14.8% in 2004 to 9.8% in 2014 (P < 0.001). Rates of cesarean section decreased from 57.3% in 2004 to 45.7% in 2014 (P < 0.001), while rates of spontaneous vaginal delivery increased from 37.4% in 2004 to 50.1% in 2014 (P < 0.001). The rate of wound complications decreased from 2.1% in 2004 to 0.4% in 2014 (P < 0.001). However, the rate of congenital anomalies increased from 0.5% in 2004 to 1.2% in 2014 (P = 0.001). CONCLUSIONS: In spite of increases in demographic risk factors associated with increased pregnancy complications, we hypothesize that the interventions made to minimize the risks of cesarean section and manage metabolic complications in women with PCOS during the period of study have resulted in improved pregnancy outcomes during the period of study.

Obstetric and perinatal outcomes in women with cerebrovascular accident vs. transient ischemic attack: an evaluation of a population database.

PURPOSE: Cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs) are uncommon neurologic events in women of childbearing age. We aimed to compare pregnancy, delivery, and neonatal outcomes between women who suffered from a CVA and those who experienced a TIA. METHODS: A retrospective population-based cohort study was performed using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample. Included were all pregnant women who delivered or had a maternal death in the US between 2004 and 2014. We compared women with an ICD-9 diagnosis of a CVA before or during pregnancy to those diagnosed with a TIA before, during the pregnancy, or during the delivery admission. Pregnancy and perinatal outcomes were compared between the two groups, using multivariate logistic regression to control for confounders. RESULTS: Among 9,096,788 women in the database, 898 met the inclusion criteria. Of them, 706 women (7.7/100,000) had a CVA diagnosis, and 192 (2.1/100,000) had a TIA diagnosis. Women with a CVA, compared to those with a TIA, had a higher rate of pregnancy-induced hypertension (aOR 3.82,95%CI 2.14-6.81, p < 0.001); preeclampsia (aOR 2.6,95%CI 1.3-5.2, p = 0.007), eclampsia (aOR 13.78,95% CI 1.84-103.41, p < 0.001); postpartum hemorrhage (aOR 4.52,95%CI 1.31-15.56, p = 0.017), blood transfusion (aOR 5.57,95%CI 1.65-18.72, p = 0.006), and maternal death (54 vs. 0 cases, 7.6% vs. 0%), with comparable neonatal outcomes. CONCLUSION: Women diagnosed with a CVA before or during pregnancy had a higher incidence of myriad maternal complications, including hypertensive disorders of pregnancy, postpartum hemorrhage, and death, compared to women with a TIA diagnosis, with comparable neonatal outcomes, stressing the different prognoses of these two conditions, and the importance of these patients' diligent follow-up and care.

Pregnancy, delivery, and neonatal outcomes among women with PCOS and endometriosis: a population database cohort.

PURPOSE: PCOS and endometriosis are independent risk factors for perinatal outcomes. Little research has evaluated the concomitant effects of these conditions, nor have studies been conducted on a population database. We sought to identify the pregnancy, delivery, and neonatal outcomes in women with polycystic ovary syndrome (PCOS) and endometriosis vs. PCOS without endometriosis. METHODS: A retrospective population-based cohort study was performed extracting data using ICD-9 codes from the HCUP-NIS Database from 2004 to 2014. Endometriosis in women with PCOS represented the study group (n = 163), and the remaining PCOS, non-endometriosis patients constituted the reference group (n = 14,719). Subjects were included once per delivery. Demographics were compared using chi-squared tests. Confounding effects in pregnancy outcomes were controlled using binary logistic regression analysis. RESULTS: Concomitant endometriosis and PCOS patients were more likely to be white (88.5% vs.71.0%, p < 0.001), with BMI < 30 kg/m2 (87.1% vs.77.8%, p < 0.004) and from lower income quartiles (27.1% vs.17.1%, p < 0.017) when compared to PCOS without endometriosis. Comparing pregnancy complication rates, placental abruption (p < 0.018, aOR 3.01, 95% CI 1.21-7.50), Cesarean section (p < 0.003, aOR 1.75, 95% CI 1.21-2.53), deep venous thromboses (p < 0.002, aOR 74.31, 95% CI 4.57-1209.21), and venous thromboembolic events (p < 0.031, aOR 10.40, 95% CI 1.24-87.37), were increased in the study group compared to the reference group. CONCLUSION: Women with PCOS and endometriosis were more likely to be white, of lower socioeconomic status, lean, and experience abruptio-placenta, cesarean deliveries, and venous thromboembolisms. Since little was previously known about the combined outcomes of PCOS and endometriosis, it is difficult to counsel patients on risks. Our findings can help clinicians manage pregnant PCOS patients with endometriosis to minimize complications such as abruptio placenta and VTE.

Pregnancy, delivery and neonatal outcomes among women with hypoparathyroidism-A population-based study.

OBJECTIVE: Data are inconclusive regarding pregnancy complications associated with maternal chronic hypoparathyroidism. Therefore, we aimed to compare pregnancy, delivery and neonatal outcomes in patients affected by chronic hypoparathyroidism to those without chronic hypoparathyroidism. DESIGN: A retrospective population-based study utilising data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database over 11 years from 2004 to 2014 inclusively. Multivariate logistic regression was used to control for confounders. PATIENTS: Patients with chronic hypoparathyroidism compared with those without. MEASUREMENTS: Obstetric and neonatal outcomes. RESULTS: We identified 204 pregnancies in mothers with chronic hypoparathyroidism and 9,096,584 pregnancies without chronic hypoparathyroidism. After adjusting for age, insurance plan type, obesity, chronic hypertension, thyroid disease, pregestational diabetes mellitus, and previous caesarean section, patients in the hypoparathyroidism group, compared with those without hypoparathyroidism, were found to have an increased rate of preterm birth (<37 weeks) (19.1% vs. 7.2%, aOR: 2.49, 95% confidence interval [CI]: 1.74-3.54, p < 0.0001, respectively); and blood transfusions (4.9% vs. 1.0%, aOR: 4.07, 95% CI: 2.15-7.73, p < -0.0001). Neonates to mothers with chronic hypoparathyroidism had a higher rate of congenital anomalies (4.4% vs. 0.4%, aOR: 6.50, 95% CI: 3.31-12.75, p < 0.0001), with comparable rates of small-for-gestational-age neonates and intrauterine foetal death. CONCLUSION: This is the largest study of chronic hypoparathyroidism in pregnancy to date. We found significant increases in the rates of preterm birth, blood transfusions and congenital anomalies in chronic hypoparathyroidism. Our findings highlight the importance of identifying chronic hypoparathyroidism as a risk factor for pregnancy and neonatal complications, although it remains unknown if maintaining calcium in the target range will mitigate these risks.

Does embryo quality at transfer affect obstetric outcomes and placental findings?

STUDY QUESTION: Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? SUMMARY ANSWER: Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. WHAT IS KNOWN ALREADY: A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P < 0.001) and more pregnancies in the poor-quality group were following frozen embryo transfer. After adjustment for confounders, poor-quality embryos were associated with a higher rate of low-lying placentas [adjusted odds ratio (aOR) 2.35, 95% CI 1.02-5.41, P = 0.04] and placentas with a higher rate of villitis of unknown etiology (aOR 2.97, 95% CI 1.17-6.66, P = 0.02), distal villous hypoplasia (aOR 3.78, 95% CI 1.20-11.38, P = 0.02), intervillous thrombosis (aOR 2.41, 95% CI 1.39-4.16, P = 0.001), multiple maternal malperfusion lesions (aOR 1.59, 95% CI 1.06-2.37, P = 0.02), and parenchymal calcifications (aOR 2.19, 95% CI 1.07-4.46, P = 0.03). LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. WIDER IMPLICATIONS OF THE FINDINGS: The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Polygenic embryo screening: are there potential maternal and fetal harms?

Polygenic embryo screening (PES) and its derivate the Embryo Health Score (EHS) have generated interest in both infertile and fertile populations due to their potential ability to select embryos with a reduced risk of disease and improved long-term health outcomes. Concerns have been raised regarding the potential harms of IVF itself, including possible epigenetic changes that may affect the health of the offspring in late adulthood, which are not fully captured in the EHS calculation. Knowledge of the potential impacts of the trophectoderm biopsy, which is a key component of the PES procedure, on the offsprings' health is limited by the heterogeneity of the population characteristics used in the published studies. Nonetheless, the literature suggests a possible increased risk of preterm delivery, birth defects and pre-eclampsia after trophectoderm biopsy. Overall, the risks of PES for prenatal and postnatal health remain uncertain, and further research is needed. Counselling patients regarding these risks before considering PES is important, to provide an understanding of the risks and benefits. This review aims to highlight some of these issues, the need for continued investigation in this area, and the importance of informed decision-making in the context of PES.

Pregnancy outcomes in women with anorexia nervosa: a population-based study and analysis of a matched cohort.

RESEARCH QUESTION: What implications does anorexia nervosa have on pregnancy outcomes in a US population? DESIGN: A retrospective, population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. A dataset of all deliveries between 2004 and 2014 inclusively was created. The population was divided into women with anorexia nervosa (n = 214) and women without anorexia nervosa (n = 9,096,574), and a cohort matched 1:4 with anorexia nervosa for age, race, medical insurance type and income quartile. Delivery and neonatal outcomes were compared between the two matched groups and with the control group of deliveries. A multivariable logistic regression analysis, controlling for statistically significant baseline characteristics, explored associations between anorexia nervosa and delivery, and neonatal outcomes. RESULTS: Compared with the entire group, women diagnosed with anorexia nervosa were more likely to be white, smokers, of higher income or diagnosed with another psychiatric disorder. In the unmatched comparison, women with anorexia nervosa had a higher frequency of preterm delivery (adjusted odds ratio [aOR] 2.98 CI 1.86 to 4.76, P < 0.001), placental abruption (aOR 3.41 CI 1.38 to 8.40, P = 0.008) and small for gestational age (SGA) neonates (aOR 5.32 CI 3.12 to 9.09, P < 0.001). In the matched comparison, preterm delivery (aOR 5.31, CI 3.02 to 9.32, P < 0.001) and SGA neonates were significantly higher in the anorexia nervosa group (aOR 4.69 CI 2.6 to 8.41, P < 0.001), providing results similar to the unmatched comparison. CONCLUSION: Healthcare providers, specifically fertility specialists, should be aware of the magnitude of adverse outcomes related to pregnancy in women with anorexia nervosa.

The relationship of smoking with gestational diabetes: a large population-based study and a matched comparison.

RESEARCH QUESTION: Is smoking associated with an increased risk for gestational diabetes (GDM)? DESIGN: A retrospective population-based study using data from the United States Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. A dataset of all deliveries that took place between 2004 and 2014 (inclusive) was created. The population was divided into two groups according to smoking status and matched 1:1 for age, obesity, race, insurance type, thyroid disease, drug use and chronic hypertension. Delivery outcomes were compared between the two matched groups and the control group of non-smokers as a whole. A multivariate logistic analysis was performed adjusting for any statistically significant confounding baseline effects not matched for. RESULTS: The study identified 9,096,788 births between 2004 and 2014, of which 443,590 (4.9%) were maternal smokers. When compared with the entire group of non-smokers as controls, there was an increased risk of GDM, adjusted odd ratio (aOR) 1.10 (95% confidence interval [CI] 1.07-1.14, P < 0.001). This relationship was of a mild nature and there were many confounding variables that differed between the groups. As such a matched control group was developed to compare the risk of GDM in the smokers and non-smokers. An increased risk for GDM among smokers remained, with an aOR of 1.07 (95% CI 1.05-1.10, P < 0.001). CONCLUSIONS: The current data suggest that smoking is a small but significant risk factor for GDM with an aOR of 1.07.

Adverse obstetric outcomes in women with PCOS and multiple gestations.

RESEARCH QUESTION: Does multiple gestation alter the risks for adverse obstetric outcomes in women with polycystic ovary syndrome (PCOS)? DESIGN: Retrospective population-based cohort study using data from the HCUP-NIS from 2004 to 2014. A total of 14,882 women with PCOS, who delivered within that time period, were identified. The study group comprised women with PCOS who had had a multiple gestation (n = 880); the reference group was comprised of the remaining women with PCOS and singleton gestation (n = 14,002). RESULTS: In women with PCOS, multiple gestation increased the risks of pregnancy complications including pregnancy-induced hypertension (adjusted odds ratio [aOR] 2.030; 95% confidence interval [CI] 1.676-2.460), pre-eclampsia (aOR 2.879; 95% CI 2.277-3.639), pre-eclampsia and eclampsia superimposed on pre-existing hypertension (aOR 1.917; 95% CI 1.266-2.903) and gestational diabetes (aOR 1.358; 95% CI 1.114-1.656). Multiple gestation increases the risk of preterm premature rupture of membranes (aOR 5.807; 95% CI 4.153-8.119), preterm delivery (aOR 8.466; 95% CI 7.071-10.135), Caesarean section (aOR 5.146; 95% CI 4.184-6.329), post-partum haemorrhage (aOR 1.540; 95% CI 1.065-2.228) and the need for transfusion (aOR 3.268; 95% CI 2.010-5.314), as well as wound complications (aOR 3.089; 95% CI 1.647-5.794). Neonates born to mothers with PCOS and having multiple gestations are more likely to be small for gestational age when compared to singleton neonates born to mothers with PCOS (aOR 4.606; 95% CI 3.480-6.095). Among PCOS women with multiple gestations, obesity increased the risks of developing pregnancy-induced hypertension (P < 0.001), pre-eclampsia (P < 0.001) and wound complications (P = 0.045). CONCLUSION: These results highlight the importance of single embryo transfer and ovulation induction to develop a single follicle in women with PCOS. Obesity further increases obstetrical complications.

The effect of oestrogen dose and duration in programmed frozen cycles on obstetric outcomes and placental findings.

RESEARCH QUESTION: Does programmed frozen embryo transfer (FET) with high-dose oestrogen affect obstetric outcomes and placental findings? DESIGN: A retrospective cohort of live singleton deliveries at a single institution between 2009 and 2017, including deliveries attained by IVF with programmed FET; oocyte recipients were excluded. High-dose oestrogen was defined as a daily dose >6 mg throughout treatment. All placentas were evaluated regardless of complication status and the Amsterdam classification was used to analyse findings. RESULTS: A total of 57 deliveries in the high-dose oestrogen group were compared with 274 controls. The high-dose oestrogen group displayed significantly longer duration of oestrogen treatment (18.8 ± 4.9 versus 13.3 ± 2.7 days, P < 0.001), total cumulative oestrogen dose (149.7 ± 46.1 versus 80.3 ± 16.8 mg, P < 0.001) and lower endometrial thickness (8.5 ± 1.4 versus 9.8 ± 1.7 mm, P < 0.001). After adjustment for confounders, higher dose oestrogen was found to be associated with a lower average birthweight (coefficient -252.4 g, 95% confidence interval [CI] -483.5 to -21.2), a higher rate of low-birthweight neonates (adjusted odds ratio [aOR] 4.88, 95% CI 1.05 to 22.57), bilobated placentas (aOR 3.36, 95% CI 1.04 to 10.89), accessory lobes (aOR 8.74, 95% CI 1.24 to 61.5), accelerated villous maturation (aOR 2.06, 95% CI 1.09 to 3.87), retroplacental haematoma (aOR 5.39, 95% CI 1.11 to 26.13) and maternal malperfusion lesions (aOR 1.46, 95% CI 1.04 to 2.05). CONCLUSION: A higher daily oestrogen dose in programmed FET is associated with low birthweight and placental changes, although this may relate to altered endometrial properties and not to the treatment itself.

TUBB8 mutations as a cause of oocyte maturation abnormalities: presentation of oocyte and embryo profiles and novel mutations.

RESEARCH QUESTION: What are the embryonic profiles and oocyte maturation dynamics in patients with tubulin beta eight class VIII (TUBB8) mutations leading to oocyte maturation abnormalities (OMAS), and are pregnancies possible in this population? DESIGN: A prospective cohort study was undertaken in a private fertility clinic between January 2019 and December 2022. Whole-exome genomic studies (WES) were performed to detect mutation types. In-vitro maturation (IVM) was compared in 18 subjects: nine with TUBB8 mutations, and nine without TUBB8 mutations to act as the control group. The distributions of oocyte maturation and embryonic development profiles were recorded. IVF and IVM outcomes of the 18 cases were evaluated. The primary outcomes were the embryonic profiles and maturation dynamics of oocytes derived from IVF or IVM in women as related to TUBB8 mutations. RESULTS: Mutations were detected in 52 of 89 (58.4%) women who underwent WES analysis. Twelve TUBB8 mutations were detected in nine women (10.1%) with OMAS. Seven novel TUBB8 mutations were noted. Two pregnancies were obtained in women with c.535 G>A TUBB8 mutations. When comparing IVM outcomes between women with and without TUBB8 mutations, there were no differences in oocyte, embryo or pregnancy parameters (P>0.05 in all cases). CONCLUSIONS: It is clear that further TUBB8 mutations which cause oocyte or embryonic arrest will be detected in future. Although biochemical or ectopic pregnancies may be possible in some of these women, no live births or ongoing pregnancies have been reported to date.