The impact of polycystic ovary syndrome on placental histopathology patterns in in-vitro fertilization singleton live births.

INTRODUCTION: Pregnant polycystic ovary syndrome (PCOS) patients are at increased risk for myriad obstetric complications, with the placenta thought to play a key role in their development. We aimed to evaluate placental histopathology patterns in placentas of women with PCOS who underwent in-vitro-fertilization (IVF). METHODS: This retrospective study utilized full gross and histopathologic assessment of placentas of all women who had IVF treatment and delivered at the Royal Victoria Hospital from 2009 to 2017, regardless of complications or mode of delivery. Pathologic findings included anatomic, inflammation, villous maturation, and vascular mal-perfusion features. Placentas of PCOS women were compared to those of ovulatory controls. Multivariate logistic regression was used to adjust results for confounding factors potentially associated with significant placental and perinatal characteristics. RESULTS: Women with PCOS (n = 47) were more likely to develop gestational diabetes mellitus compared to ovulatory controls (n = 1121) (38.3% vs. 9.8%, p < 0.001). Placentas from PCOS women were more likely circumvallate placentas (aOR 8.3, 95%CI 1.9-37.3) and more likely to have a hypercoiled umbilical cord (aOR 6.8 95%CI 1.3-36.8) and villitis of unknown etiology (aOR 6.1, 95%CI 1.5-25.6). There was an increased likelihood of chorangiosis (aOR 2.7, 95% CI 1.3-5.8), evidence of fetal vascular malperfusion based on one criteria (aOR 2.7, 95%CI 1.1-7.4), or more than one criteria (aOR 6.4, 95%CI 1.6-25.9), more nucleated fetal red blood cells (aOR 5.2, 95%CI 1.1-24.5), and a higher likelihood of chorangiomas (aOR 9.4, 95%CI 1.6-55.1) in placentas from PCOS women than in controls. DISCUSSION: IVF pregnancies' placental histopathological characteristics are significantly impacted by an underlying diagnosis of PCOS, including important anatomic changes and vascular placental abnormalities.

Relationship between the follicular distribution pattern of polycystic ovaries and the degree of menstrual disturbance and serum sex steroid levels.

Objective: This study aimed to examine the associations between follicular distribution pattern (FDP) in polycystic ovaries and menstrual disturbances in women with infertility. Materials and Methods: A retrospective review of patients was performed (n=73). Ultrasound images from cycle day 2-5 of a spontaneous or progestin induced menstrual cycle were reviewed. Ovaries were classified as polycystic ovarian morphology (PCOM) if they contained ≥12-follicles measuring 2-9 mm in diameter. Images of PCOM ovaries were classified as having a peripheral cystic pattern (PCP) with follicles arranged at the periphery of the ovary, or general cystic pattern (GCP) if follicles were dispersed heterogeneously throughout the ovarian stroma. Menstrual disturbance was assessed by questionnaire, and oligomenorrhea was defined as cycles >35 days in length. Results: PCP was more strongly associated with menstrual irregularity that GCP. 94% of subjects with bilateral PCP-experienced oligomenorrhea compared with 65% of women with a unilateral PCP ovary [odds ratio (OR) 9; p<0.05]. 29% of women with bilateral GCP ovaries experienced menstrual disturbances, less than bilateral PCP (OR 36; p=0.002), but similar to unilateral PCP (OR 3; p=0.07). Serum testosterone and luteinizing hormone (LH) levels were significantly correlated with the ovarian FDP. Conclusion: There is a relationship between menstrual irregularity or certain types of serum steroids and ovarian morphology. It remains unknown if morphology, testosterone or LH causes the menstrual disturbance or if they are co-initiated by an intervening factor.

Gonadotropin releasing hormone (GnRH) antagonist administration to decrease the risk of ovarian hyperstimulation syndrome in GNRH agonist cycles triggered with human chorionic gonadotropin.

PURPOSE: In Gonadotropin releasing hormone(GnRH) agonist IVF, after administration of human chorionic gonadotropin(HCG) triggering, there is a risk of ovarian hyperstimulation syndrome(OHSS). Few methods exist to prevent OHSS in these cases. Therefore, we investigated the use of a GnRH antagonist to decrease the risk of OHSS, due to its ability to decrease VEGF production and function. METHOD: A retrospective cohort study of 171-IVF patients at risk for developing OHSS after a GnRH agonist cycle with HCG trigger was performed from 2011 to 2019. The patient population consisted of women with an unexpected exuberant response to stimulation based on ovarian reserve testing and were triggered with hCG. Women were converted to a freeze-all cycle and received either cabergoline 0.5 mg orally alone for 7 days from the collection(Group 1, n = 123) or received cabergoline 0.5 mg orally and ganirelix, 250 mcg SC for 7-10 days(Group 2, n = 48). RESULTS: Group 1 had more cases of moderate and severe OHSS than group 2-(25% vs. 10% p = 0.03, and 52% vs. 25% p = 0.001 respectively). Group 1 reported more abdominal discomfort and bloating than group 2(91% vs. 65% p < 0.001) and the presence of free fluid was more frequent in group 1 than group 2(74% vs. 35% p < 0.001). Hemoconcentration and electrolyte disturbances were less severe in group 2 than in group 1 (p < 0.001 all cases). CONCLUSION: In patients at high risk for developing OHSS after hCG trigger in a GnRH agonist cycle, the addition of GnRH antagonists in the luteal phase may reduce the risk of developing moderate and severe OHSS. The GnRH antagonist likely leads to more rapid luteolysis and down regulation of VEGF production and receptor response, thereby decreasing the hallmark increased vascular permeability.

Transvaginal Sonography Post-Office Hysteroscopy as a Screening Tool for Tubal Patency: A Reliable and Feasible Technique in an Outpatient Setting.

OBJECTIVE: To determine feasibility and accuracy of post-hysteroscopic transvaginal ultrasonography (TVUS) measurement of pelvic fluid accumulation as a screening method for tubal patency (TP). METHODS: We conducted a retrospective cohort study of 85 patients who underwent uterine cavity assessment by office hysteroscopy at our university-affiliated fertility centre from November 2019 to October 2020. During the study period, two-dimensional (2D) TVUS was performed pre- and post-hysteroscopy to evaluate TP. Patient records were reviewed for demographics, diagnosis, and prior/subsequent TP testing. Predictive values for TP were calculated. RESULTS: Pelvic fluid accumulation post-hysteroscopy was found in 65.9% of patients (56). Accumulation of fluid was seen with the use of as little as 10-50 mL of saline. Using more fluid did not increase the likelihood of demonstrating TP (P = 0.17). A trend towards more false-negative results for TP was observed when less fluid was used (7.7% with 10-50 mL vs. 3.8% with 60-190 mL and 1.3% with 200-760 mL; P = 0.10). The positive predictive value (PPV) of TVUS post-hysteroscopy in comparison to known patency/occlusion was 100%; negative predictive value (NPV) was 33%; sensitivity was 82.8%; and specificity was 100%. Similar values were seen in a second analysis that included patients with highly suspected patent or occluded tubes (n = 60); presumed predictive values were: PPV 100%, NPV 42%, sensitivity 78.8%, and specificity 100%. The use of more fluid did not increase pain (P = 0.75). This finding remains after accounting for confounders (e.g., pre-medication, endometrial biopsy). CONCLUSION: TVUS pre- and post-hysteroscopy is feasible in an outpatient setting, and can serve as a reliable screening tool for TP. When hysteroscopy is performed and TP is not known, TVUS can be added for screening, potentially omitting the need for more invasive examinations. With limited non-urgent ambulatory services, it is of upmost importance to maximize information from a single procedure.

Three hour abstinence as a treatment for high sperm DNA fragmentation: a prospective cohort study.

PURPOSE: This study sought to compare sperm DNA fragmentation (SDF) in semen specimens after 3 days and then after 3 h of abstinence in men presenting for initial infertility evaluation. METHODS: A prospective cohort study of 112 men undergoing their first semen analysis as part of an infertility work-up was conducted. All participants presented with 3 days of abstinence for a semen analysis and DNA-fragmentation test. Both tests were repeated on a second sample collected 3 h after the first ejaculation. DNA-fragmentation was evaluated with the halo test by one of two technicians blinded to duration of abstinence. Variables analyzed include ejaculate volume, sperm concentration and motility, smoking status, cannabis use, initial specimen DNA fragmentation, and use of sperm-directed anti-oxidant formulations. RESULTS: Among all subjects, DNA fragmentation improved in the 3-h abstinence specimen (34.6 ± 19.4% vs. 23.7 ± 16.0%, p = 0.0001). Among subjects with high DNA fragmentation (> 35%) on the initial specimen, 55% improved into the normal range. Semen volume and sperm concentration decreased (3.1 ± 3.3 ml vs. 1.9 ± 0.8 ml, p < 0.01 and 41 ± 39 vs. 32 ± 31 (millions/ml), p = 0.01), while progressive motility tended to increase. Fifty-eight subjects demonstrated ≥ 30% improvement in SDF in the second specimen as compared to the first. Factors found to correlate with > 30% improvement in DNA fragmentation in the 3-h abstinence specimen compared to 3 days were younger age and use of anti-oxidants. CONCLUSION: High SDF can often be managed with a second ejaculation 3 h after the first in infertile couples, including in males with abnormal semen analyses per the 2010 WHO guide. Apart from SDF levels, changes in sperm quality were not clinically significant in the second specimen and did not increase rates of ICSI. However, a second ejaculation after 3 h probably may reduce the necessity of costly and/or invasive ART strategies.

Associations between polycystic ovary syndrome and adverse obstetric and neonatal outcomes: a population study of 9.1 million births.

STUDY QUESTION: Does polycystic ovary syndrome (PCOS) confer an independent risk for adverse delivery and neonatal outcomes, based on analysis of the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database? SUMMARY ANSWER: After controlling for all potential confounding effects, women with PCOS are at an increased risk of experiencing preterm pre-labour rupture of membranes (PPROM), pre-term delivery (PTD), placental abruption, caesarean section (C/S) delivery, chorioamnionitis and post-partum maternal infections. WHAT IS KNOWN ALREADY: PCOS may be associated with an increased risk of adverse perinatal outcomes. However, there remain significant gaps in understanding the correlation between PCOS and important delivery and neonatal complications. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based cohort study utilising data from the HCUP-NIS over 11 years from 2004 to 2014. A cohort of all deliveries between 2004 and 2014 inclusively was created. Within this group, all deliveries to women with PCOS were identified as part of the study group (n = 14 882), and the remaining deliveries were categorised as non-PCOS births and comprised the reference group (n = 9 081 906). PARTICIPANTS/MATERIALS, SETTING, METHODS: The HCUP-NIS is the largest inpatient sample database in the USA and it is comprised of hospital inpatient stays throughout the entire country. It provides information relating to 7 million inpatient stays per year, includes ∼20% of admissions, and represents over 96% of the American population. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for all potential confounders, women with PCOS were more likely to experience PPROM (aOR 1.48, 95% CI 1.20-1.83), PTD (aOR 1.37 95% CI 1.24-1.53) and placental abruption (aOR 1.63, 95% CI 1.30-2.05) and were more likely to deliver by C/S (aOR 1.50, 95% CI 1.40-1.61 (all P < 0.001). Women with PCOS more often developed chorioamnionitis (aOR 1.58, 95% CI 1.34-1.86, P < 0.001) and maternal infections (aOR 1.58, 95% CI 1.36-1.84 (both P < 0.001)). With the exception of multiple gestations (aOR 1.27, 95% CI 1.01-1.62, P = 0.04), there was no difference in the number of women who gave birth to small for gestational age (SGA) infants (aOR 0.97, 95% CI 0.82-1.15, P = 0.72) between the women with PCOS and the reference group. Intrauterine foetal deaths (IUFDs) were also comparable between the two groups (aOR 1.03, 95% CI 0.68-1.59, P = 0.88). However, congenital anomalies were more likely to occur in the offspring of women with PCOS (aOR 1.89, 95% CI 1.51-2.38, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective analysis utilising an administrative database which relies on the accuracy and consistency of the individuals coding the data. There are known limitations in how accurately hospital coding is able to capture perinatal conditions and complications, making it difficult to know with certainty that such events are accurate. WIDER IMPLICATIONS OF THE FINDINGS: Women with PCOS are more likely to experience adverse delivery and neonatal outcomes. It is important to additionally consider the risk of all other co-existing conditions frequently encountered in PCOS women, as these risks are additive and place women with PCOS at significantly increased risk of adverse pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. The authors have no conflicts of interest to disclose.

Polycystic ovary syndrome as an independent risk factor for gestational diabetes and hypertensive disorders of pregnancy: a population-based study on 9.1 million pregnancies.

STUDY QUESTION: Does polycystic ovary syndrome (PCOS) confer an independent risk for the development of gestational diabetes mellitus (GDM), gestational hypertension (GHTN) and preeclampsia (PEC) based on analysis of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database. SUMMARY ANSWER: After controlling for all potential confounding effects, women with PCOS are at a 2-fold higher risk of developing GDM, a 50% increased risk for the development of GHTN and a 30% increased risk of developing PEC than women without PCOS. WHAT IS KNOWN ALREADY: Currently, there is evidence of an increased prevalence of maternal pregnancy complications in women with PCOS. However, there remain significant gaps in understanding how PCOS affects the development of GDM, GHTN and PEC. This is most likely due to the complex, multifactorial etiology of PCOS, its range of potential confounders for pregnancy complications and the variable methodology of studies that have been conducted. To date, the largest meta-analysis on this subject includes 11 565 women with PCOS analyzed for their risk of GDM and 5896 patients analyzed for their risk of PEC. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based study utilizing data from the HCUP-NIS over 11 years from 2004 to 2014. A dataset of all deliveries between 2004 and 2014 inclusively was created. Within this group, all deliveries to women with PCOS were identified as part of the study group (n = 14 882), and the remaining deliveries were categorized as non-PCOS births and comprised the reference group (n = 9 081 906). PARTICIPANTS/MATERIALS, SETTING, METHODS: The HCUP-NIS is the largest inpatient sample database in the USA and is comprised of hospital inpatient stays submitted by hospitals throughout the entire country. Each year, the database provides information relating to 7 million inpatient stays, including patient characteristics, diagnosis and procedures. The data are representative of ∼20% of admissions to US hospitals across 48 states and the District of Columbia. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, more pregnant women with PCOS were obese (22.3% vs. 3.5%, P < 0.001), had chronic hypertension (HTN) (8.4% vs. 1.8%, P < 0.001), had pregestational diabetes (4.1% vs. 0.9%, P < 0.001) and had treated thyroid disease (12.6% vs. 2.4%, P < 0.001). Women with PCOS were also more likely to have undergone IVF treatment (2.4% vs. 0.1%, P < 0.001), have multi-gestation pregnancies (5.9% vs. 1.5%, P < 0.001), and more multiple gestations (MGs) in the PCOS group were the result of IVF treatment than the non-PCOS groups (12.3% vs. 2.3%, P < 0.001). In all pregnancies, women with PCOS were more likely to develop gestational diabetes (adjusted odds ratio (aOR) 2.19, 95% CI 2.02-2.37), pregnancy associated HTN (aOR 1.38, 95% CI 1.27-1.50, P < 0.001), GHTN (aOR 1.47, 95% CI 1.31-1.64), PEC (aOR 1.29, 95% CI 1.14-1.45) and superimposed PEC (aOR 1.29, 95% CI 1.04-1.59) after controlling for confounding effects (age, race, income level, insurance type, obesity, IVF use, previous cesarean section, chronic HTN, pregestational diabetes, thyroid disease, MG, smoking and recreational drug use). Odds ratios were comparable between all pregnancies and singleton pregnancies only. In women pregnant with multiple fetuses, PCOS only conferred a statistically significant increased risk of developing GDM (aOR 2.33, 95% CI 1.92-2.83, P < 0.001). However, there was a trend toward an increased risk for developing pregnancy associated HTN (aOR 1.92, 95% CI 0.99-1.42, P = 0.058). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective analysis utilizing an administrative database which relies on the accuracy and consistency of the individuals coding the data. There are known limitations in how accurately hospital coding is able to capture perinatal conditions and complications, making it difficult to know with certainty that such events are accurate. WIDER IMPLICATIONS OF THE FINDINGS: Pregnant women with PCOS are at increased risk of adverse complications in pregnancy even when they do not present with other coexisting metabolic conditions. Furthermore, it is important to also consider the risk of all other coexisting metabolic conditions frequently encountered in PCOS women, as these risks are additive and place women with PCOS at significantly increased risk for adverse complications in pregnancy. STUDY FUNDING/COMPETING INTEREST(S): None.

Myometrial Pseudoaneurysm and Myelosuppression Following Conservative Management of Cesarean Scar Ectopic Pregnancy.

BACKGROUND: Treatment of cesarean scar pregnancy is based on clinical context. This report describes two rare complications of conservative management: non-steroidal anti-inflammatory drug-induced methotrexate myelosuppression and myometrial pseudoaneurysm. CASE: A 34-year-old woman was treated conservatively for a cesarean scar pregnancy with systemic methotrexate and intragestational potassium chloride, resulting in pancytopenia secondary to concurrent non-steroidal anti-inflammatory drug use. She presented again with a myometrial pseudoaneurysm, which was treated with bilateral uterine artery embolization and, ultimately, hysterectomy. The final pathology report confirmed a pseudoaneurysm, retained villi within the myometrium, and acute endometritis and myometritis. CONCLUSION: Myelosuppression resulting from use of non-steroidal anti-inflammatory drugs affecting renal excretion of methotrexate can occur at low dosages. Additionally, there is a risk of pseudoaneurysms with vascular damage and trophoblastic tissue. Drug interactions and procedure-related risks must be considered when managing cesarean scar pregnancy conservatively.