Role of probiotic as adjuvant in treating various infections: a systematic review and meta-analysis.

BACKGROUND: Research on the advantages of probiotics has attracted increasing interest based on the number of publications, products, and public awareness of their benefits. This review evaluated the role of probiotics (single and multiple regimens) as an additional regimen to treat common infectious diseases, including Helicobacter. pylori, diarrheal infections, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and HIV infections. METHODS: We searched randomized controlled trials from PubMed, Scopus, Embase, and Cochrane and identified 6,950 studies. Duplicates were removed, and titles and abstracts were filtered. Bias was evaluated using the Cochrane Risk of Bias Tool for Randomized Trials (ROB 1.0 and 2.0). The certainty of the evidence was evaluated using GRADE. Data were extracted and meta-analysis was performed using RevMan. RESULTS: A total of 32 studies were included in this study (22 H. pylori studies, 2 diarrheal infection studies, 6 UTI studies, and 2 HIV infection studies). There was no study on URTI. Probiotics, in addition to primary treatment, could improve the eradication of H. pylori versus the control (RR: 1.09; 95% CI:1.04 - 1.13, p value = 0.001) and achieve a cure range of Nugent score in UTI patients (RR 1.38; 95% CI: 1.01 - 1.89, p value = 0.04). For eradicating H. pylori infection, subgroup analysis based on the therapy regimen showed that standard triple therapy was slightly superior compared to quadruple therapy in eradicating H. pylori (RR: 1.14 vs. 1.01, respectively). Single strain probiotics showed a similar effect to multiple strain probiotic regimens (both had an RR of 1.09). The effect estimates of the use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI had a high certainty of evidence. Meta-analysis was not performed for infectious diarrheal because there were only two eligible studies with different probiotic supplementations and outcome parameters. Nonetheless, they showed that the diarrheal incidence was lower and complete remission of diarrheal was higher after the regimen of probiotics. Similarly, a meta-analysis was not performed for HIV infection because the two eligible studies used different designs and comparators with contradicting findings. CONCLUSION: This meta-analysis showed beneficial use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI. Probiotic supplementation might not be beneficial for patients given a quadruple therapy. Single-strain and multi-strain probiotic regimens had similar effects in increasing the eradication rate of H. pylori. Our study also suggested that the benefits of probiotics as an additional regimen in infectious diarrheal and HIV infections remain unclear; more studies are needed to confirm the benefits.

Psychosocial impacts, preventive behaviours, and concerns associated with the COVID-19 pandemic for pregnant and non-pregnant women: A matched analysis from the International iCARE Study.

BACKGROUND:  The COVID-19 pandemic negatively affected physical and psychological health worldwide. Pregnant women were likely more vulnerable to mental health difficulties due to the significant social, psychological, and hormonal changes they experience. During the pandemic, higher rates of antenatal depression and anxiety were observed compared to pre-pandemic rates. Increased mental health symptoms in pregnancy have been associated with adverse outcomes for child development. Understanding pandemic-specific preventive behaviours (i.e., mask use, physical distancing) and concerns may also be linked to maternal psychological well-being. PURPOSE: To compare matched pregnant and non-pregnant women (N = 474) to assess COVID-19 psychosocial impacts, preventive behaviours, and concerns. METHODS: This study used a matched analysis of data collected by the International COVID-19 Awareness and Responses Evaluation (iCARE) Study. Participants were matched on several demographic factors and analyses were adjusted for chronic illness and psychiatric disorder. RESULTS: Linear regression analyses indicated that pregnant women did not significantly differ from matched non-pregnant women for psychosocial impacts (B = 0.11, SE = 0.08, p = 0.178). Those who reported a chronic illness (B=-0.19, SE = 0.09, p = 0.036) or a psychiatric disorder (B=-0.28, SE = 0.09, p = 0.003) were more likely to report more significant psychosocial impacts. Logistic regression analyses indicated that pregnant women were more likely to report staying at home rather than going to work (OR = 2.01, 95% CI 1.31-3.08, p = 0.002) and being concerned about being infected (OR = 1.61, 95% CI 1.05-2.46, p = 0.028). CONCLUSIONS: Our findings in the context of the COVID-19 pandemic highlight the need to consider interventions targeting women, with chronic illnesses or psychiatric disorders, as they are often the most vulnerable.

The Blastulation Rate Is Negatively Associated With Euploid Rate.

OBJECTIVES: To study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts. METHODS: A cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study. RESULTS: A total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio. CONCLUSIONS: This study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted.

Perioperative complication rates of colpocleisis performed with or without concomitant hysterectomy: a large population-based study.

INTRODUCTION AND HYPOTHESIS: We aimed to compare perioperative complications for women who underwent colpocleisis with and without concomitant hysterectomy, and report the rate of concomitant hysterectomy. METHODS: We conducted a retrospective study using the Healthcare Cost and Utilization Project (HCUP) - Nationwide Inpatient Sample 2004 to 2014. We used International Classification of Diseases, Ninth Revision (ICD-9) codes to identify women with pelvic organ prolapse (POP) who underwent colpocleisis with or without concomitant hysterectomy. Trend over time of each procedure type was created. We calculated odds ratios (ORs) to determine the risk of perioperative complications with or without concomitant hysterectomy. ORs were adjusted for age, race, income, insurance plan, and hypertension. RESULTS: Of 253,100 adult women who underwent POP repair, 7,431 had colpocleisis. Colpocleisis with concomitant hysterectomy was performed in 1,656 (22.2%) and 5,775 (77.7%) underwent colpocleisis alone (2,469 [33.2%] had a previous hysterectomy). Hysterectomy rates among women with POP undergoing colpocleisis remained relatively steady, whereas those undergoing colpocleisis without hysterectomy declined over time. Prevalence of any complications was higher among those with concomitant hysterectomy (11.4% vs 9.5%, p=0.023). Adjusted OR showed that concomitant hysterectomy increased the risk of complications (OR 1.93, 95% CI 1.45-2.57, p<0.001). CONCLUSIONS: Our large administrative data analysis suggests an increased risk of complications when performing a hysterectomy at the time of colpocleisis. A concomitant hysterectomy was performed in 22% of cases. Whether or not to include hysterectomy at the time of colpocleisis is based on shared decision making, influenced by individual patients' values, comorbidities, and risk of complications.

Association between Endometriosis and Risk of Preeclampsia in Women Who Conceived Spontaneously: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the association between endometriosis and the risk of preeclampsia and other maternal outcomes in spontaneously conceived women. DATA SOURCES: PubMed, MEDLINE, Embase, Scopus, Cochrane Library, Web of Science, and Google Scholar were systemically searched for studies published from inception to November 2021 (CRD42020198741). Observational studies published in English or French that investigated the risk of preeclampsia in women with endometriosis who conceived spontaneously were included. METHODS OF STUDY SELECTION: A total of 610 articles were reviewed once duplicates were removed. Inclusion criteria included spontaneous conception and surgical and/or imaging ascertainment of an endometriosis diagnosis. Exclusion criteria included conception using assisted reproductive technologies, multiple pregnancies, chronic hypertension, and unclear diagnoses of endometriosis. TABULATION, INTEGRATION, AND RESULTS: Data of selected studies were extracted, and analysis was performed on Review Manager, version 5.4. Quality assessment of included studies for potential risk of bias was evaluated using the Newcastle-Ottawa Scale for cohort studies. Three cohort studies of spontaneous pregnancies were included. Endometriosis was associated with an increased risk of preeclampsia (risk ratio [RR] = 1.47, 95% CI 1.13 -1.89, p = .003; I2 = 0%; n = 3 studies). A sensitivity analysis excluding a study with adenomyosis cases yielded similar risk (RR = 1.44; 95% CI, 1.11-1.87; p = .006; I2 = 0%; n = 2 studies). Having endometriosis did not significantly increase risk of cesarean delivery (RR = 1.38; 95% CI, 0.99-1.92; p = .06; I2 = 80%; n = 2 studies) or postpartum hemorrhage (RR = 1.16; 95% CI, 0.46-2.91; p = .76; I2 = 50%; n = 2 studies). CONCLUSION: We detected an increased risk of preeclampsia in women with endometriosis who conceived spontaneously. Endometriosis did not seem to increase the risk of cesarean delivery and postpartum hemorrhage, but the number of studies was limited, and the heterogeneity was high.

Identifying Targets to Improve the Management of Severe Hypertension in Pregnancy and Postpartum.

OBJECTIVES: To (1) define quality indicators, (2) describe care gaps, and (3) identify process issues in severe hypertension (sustained systolic blood pressure [BP] ≥160 mm Hg or diastolic BP ≥110 mm Hg) management at our tertiary care centre. METHODS: Pregnant and postpartum persons diagnosed with a hypertensive disorder of pregnancy from 2018 to 2019 were identified. A retrospective cohort of patients with severe hypertension was constructed, and data were collected through chart review. Severe hypertension management was assessed according to defined quality indicators. Clinical characteristics were compared between participants with and without time-to-target BP within 60 minutes. Process issues were examined for each severe hypertension occurrence. RESULTS: Of 608 participants with a hypertensive disorder of pregnancy, 90 (15%) experienced severe hypertension. Median time-to-target BP was 76 minutes (interquartile range 47-123 minutes), and target BP (<155/105 mm Hg) was achieved within 60 minutes in 31/90 (34%) participants. Appropriate antihypertensives for severe hypertension were used in 55/90 (61%), and time-to-treatment initiation was within 30 minutes in 42/54 (78%). Chronic hypertension and oral labetalol use were associated with delays in achieving target BP. Process issues related to severe hypertension management included inappropriate treatment (n = 35/90; 39%), failure to recognize severe hypertension as an emergency (n = 21/90; 23%), and delayed treatment initiation (n = 12/54; 22%). CONCLUSION: We defined quality indicators for severe hypertension management. Time-to-target BP within 60 minutes was achieved in a minority of patients, and chronic hypertension was associated with delayed severe hypertension resolution. Process issues in severe hypertension management were described.

Postoperative Discharge Opioid Consumption, Leftover, and Disposal after Obstetric and Gynecologic Procedures: A Systematic Review.

OBJECTIVE: To perform a systematic review on consumption, leftover, and disposal of prescribed opioids after surgery in obstetrics and gynecology (The International Prospective Register of Systematic Reviews ID 249856). DATA SOURCES: Electronic database searches on PubMed, Embase, Cochrane Library, and MEDLINE and other search methods including all studies published between the years 2000 and 2021 were used. METHODS OF STUDY SELECTION: We included all randomized trials, cohorts, case-control studies, and clinical trials. The search was limited to studies related to obstetrics and gynecology. Studies that pertained to opioid consumption, leftover, and disposal patterns were selected. We excluded review articles, meeting abstracts, case series and case reports, and abstracts without access to full texts. The search was limited to trials in humans and published in English language. Study population included women who were prescribed opioids after obstetric and/or gynecologic procedures. Information on opioid consumption, leftover, and disposal patterns were extracted and compared among different procedures. Potential risk of bias was evaluated using the Newcastle-Ottawa Scale for cohort studies and the National Heart, Lung, and Blood Institute Study Quality Assessment Tool of Controlled Interventional Studies for clinical trial. TABULATION, INTEGRATION, AND RESULTS: Of 2343 articles, 10 were used in the analysis: 9 cohorts and 1 randomized clinical trial. We found that among patients who underwent obstetric and gynecologic procedures, a considerable number of opioids are unused. The total number of consumed opioids after discharge in patients who underwent cesarean delivery was 21.8 oral morphine equivalent (OME); vaginal hysterectomy, 55.7 OME; abdominal hysterectomy, 105.8 OME; and laparoscopic hysterectomy, 89.0 OME. The number of opioids leftover in the vaginal, abdominal, and laparoscopic hysterectomy groups was 67.6 OME, 115.5 OME, and 95.3 OME, respectively. On average, 77.5% of leftover opioids were not disposed/kept, whereas only 20% discarded their medication through a disposal program. Five studies were deemed to have fair quality, and the rest were rated as good quality. CONCLUSION: Compared with those after cesarean delivery, patients undergoing gynecologic procedures consumed a large number of opioids, especially after abdominal hysterectomies. Abdominal hysterectomy was also associated with a high number of opioids leftover. Most patients did not use the entire prescribed opioids and were either keeping their unused opioids or unsure about what to do with them. We recommend perioperative opioid-specific counseling and education on opioid consumption, potential hazards of unused medication, and proper disposal for patients. Strategies to reduce opioids prescription by physicians should be considered.

Is There an Association Between Sperm Parameters and Sexual Orientation? A Cross Sectional Study.

OBJECTIVE: To evaluate whether sexual orientation affects sperm parameters. METHODS: This was a cross-sectional study using existing data from an academic reproductive centre for the period of April 01, 2009, to March 31, 2021. We compared the results of sperm analysis from male patients who were in same-sex relationships (study group) with those of men in heterosexual relationships who did not have male-factor infertility (control group). A subsequently comparison of both groups with World Health Organization (WHO) reference values was also performed. RESULTS: Thirty-nine samples from the study group were compared with 494 samples from the control group. All parameters, apart from morphology, were comparable. The median sperm concentrations were 64 (interquartile range [IQR] 32.1-102.9) million/mL and 50.1 (IQR 25.3-92.5) million/mL in the study and control groups, respectively (P = 0.252), whereas the median percentage of progressive motile sperm was 50% (IQR 34-65) in the study group and 52% (IQR 33-65) in the control group (P = 0.198). The median percentage of morphologically normal sperm was higher in the control group than in the study group (6% vs. 5%; P = 0.019). However, no significant difference was found when sperm morphology was dichotomized with the cut-off of ≥4% (74.1% and 74.4%, respectively; P = 0.966). When compared with the WHO reference group, the percentage of men with total motile sperm counts ≥10 million and the percentage of men with normal morphology were significantly lower in both groups. CONCLUSION: Our study suggests that there is no relationship between sexual orientation and sperm parameters.

Does increasing estrogen dose during frozen embryo transfer affect pregnancy rate?

OBJECTIVE: To assess the effect of increasing estrogen doses during hormone therapy frozen embryo transfer (HT-FET) cycles on endometrial thickness and success rates compared to patients who received fixed estrogen dose. MATERIALS AND METHODS: A retrospective study from a university-based fertility clinic during the years 2008-2021. We compared two groups: the fixed-dose group (i.e., received 6 mg estradiol dose daily until embryo transfer) and the increased-dose group (i.e., the initial estradiol dose was 6 mg daily, and was increased during the cycle). PRIMARY OUTCOME: clinical pregnancy rate. RESULTS: The study included 5452 cycles of HT-FET: 4774 cycles in the fixed-dose group and 678 cycles in the increased-dose group. Ultrasound scan on days 2-3 of the cycle showed endometrial thickness slightly different between the two groups (4.2 mm in the fixed-dose and 4.0 mm in the increased-dose group, P = 0.003). The total estrogen dose was higher, and the treatment duration was longer in the increased than the fixed-dose group (122 mg vs. 66 mg and 17 days vs. 11 days, respectively; P < 0.001). The last ultrasound scan done before the addition of progesterone showed that the endometrial thickness was significantly thicker in the fixed than the increased-dose group (9.5 mm vs. 8.3 mm; P < 0.001). The clinical pregnancy rates were 35.8% in the increased-group vs. 34.1% in the fixed-dose group; P = 0.401. CONCLUSIONS: The increased-dose group had thinner endometrium despite the higher doses of estrogen and longer treatment duration than the fixed-dose group. However, the pregnancy rates were similar between the two groups.

Conversion rate of laparoscopic or robotic to open sacrocolpopexy: are there associated factors and complications?

OBJECTIVES: To evaluate the conversion rate of laparoscopic or robotic to open sacrocolpopexy and to identify associated factors in a large population-based database. METHODS: We used Health Care Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) databases 2005-2014. We extracted data on apical suspension and synthetic mesh with laparoscopy or robot in adult women using International Classification of Diseases, ninth edition, Clinical Modification (ICD-9-CM) codes. We evaluated the rate of conversion and used logistic regression to study the association with risk factors. RESULTS: We identified 3295 women with laparoscopic or robotic sacrocolpopexies. There were 2777 robotic procedures with 37 conversion (1.33%) and 518 laparoscopic procedures with 37 conversions (7.14%), with an overall conversion rate of 2.2%. Median age was 62 years [interquartile range (IQR) = 55-69]. Concomitant hysterectomy was significantly more frequent in the robotic than laparascopic group (41.7% versus 13.9%, p < 0.01) and was not associated with conversion. Factors associated with lower conversion included a robotic approach (adjusted odd ratio (aOR) 0.32 [95% CI 0.19-0.54]) and private insurance (aOR 0.53 [95% CI 0.32-0.86]). Factors associated with higher conversion were obesity (aOR 3.27 [95% CI 1.72-6.19]) and lysis of adhesions (aOR 3.32 [95% CI 1.89-5.85]). Accidental organ puncture was significantly associated with conversion (14.9% versus 3.8%; p < 0.01). CONCLUSION: In this American database, the rate of conversion of laparoscopic or robotic to open sacrocolpopexy was low. The majority (84%) of minimally invasive sacrocolpopexies used a robotic approach, which was associated with a lower risk of conversion. Obesity and lysis of adhesions were associated with a higher risk of conversion.

Management of Hydrosalpinx in the Era of Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the effect of hydrosalpinx on pregnancy outcomes, to compare different types of management of hydrosalpinx and their impact on pregnancy rates as well as on the ovarian reserve. DATA SOURCES: Electronic search using Pubmed, EMBASE, Ovid MEDLINE, Google Scholar, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials and including all published studies that examined tubal infertility and its management (assisted reproductive technology or surgery) as well as the effects on ovarian reserve. The following medical subject headings (Mesh) terms combinations were used: "fallopian tube disease," hydrosalpinx," "tubal or salpinx occlusion or obstruction," "in vitro fertilization," "fallopian tube surgery," "salpingectomy," "salpingostomy," "infertility," "subfertility," "sterility" and "ovarian reserve." METHODS OF STUDY SELECTION: All randomized trials, cohort, and case controls studies were included. We excluded review articles, meeting abstracts, case series and case reports, and abstracts without access to full texts. The search was limited to trials in humans and published in English. TABULATION, INTEGRATION, AND RESULTS: Our electronic search initially retrieved 6354 articles. Finally, 19 studies were included in the quantitative evaluation of the effects of hydrosalpinx: 23 in the qualitative evaluation and 5 in the quantitative evaluation of different types of hydrosalpinx treatments; and 17 in the quantitative evaluation of ovarian reserve. The presence of a hydrosalpinx was associated with decreased rates of implantation and clinical pregnancy, and increased rates of ectopic pregnancy and miscarriage. Management of hydrosalpinx with salpingectomy, tubal occlusion, or hydrosalpinx aspiration led to better in vitro fertilization pregnancy rates. We found no difference in ovarian response to stimulation after salpingectomy except a decrease in antimüllerian hormone compared to no surgery. CONCLUSIONS: The presence of hydrosalpinx is associated with decreased pregnancy rate and increased rates of ectopic pregnancy and miscarriage. Management of hydrosalpinx, regardless of the type of treatment, leads to an increased chance of pregnancy.

Evaluation of Open-Access Journals in Obstetrics and Gynaecology.

A retrospective observational study was conducted to evaluate open-access journals in obstetrics and gynaecology, published between 2011 and 2019. Journals were classified based on their registration in open-access journal directories. Of 176 journals, 47 were not registered. Journals registered in the Directory of Open Access Journals (DOAJ) demonstrated good overall quality, and their journal metrics were significantly higher than those of non-registered journals or journals registered in other directories. The lack of editor names and indexing information on a journal's website are the most distinctive features of non-registered journals. Non-registration in an open-access journal directory indicates a lack of transparency and may ultimately indicate that a journal is predatory.

Association Between Bowel Obstruction or Intussusception and Endometriosis.

OBJECTIVE: To evaluate the association between endometriosis and bowel obstruction or intussusception using a large population database. METHODS: This was a population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) from 2005 to 2014. We studied women aged 18 to 55 years without inflammatory bowel disease or cancer. Multivariate logistic regression was used to examine the association between endometriosis and bowel obstruction. RESULTS: Of the 18 427 520 women who met the criteria for inclusion, 96 539 had experienced bowel obstruction, for an overall prevalence of 52 per 10 000, and 3825 had experienced intussusception, for an overall prevalence of 2 per 10 000. When adjusted for sociodemographic characteristics, women with pelvic endometriosis had a consistently higher likelihood of bowel obstruction (odds ratio [OR] 2.6; 95% confidendence interval [CI] 2.3-3.00, P <0.01). In particular, intestinal endometriosis was associated with a 14.6-fold increased risk of bowel obstruction (95% CI 11.4-18.8, P <0.01), while rectovaginal endometriosis was associated with a 2.00-fold increased risk (95% CI 1.5-2.6, P <0.01). Pelvic endometriosis was significantly associated with adhesive bowel obstruction (adjusted OR: 3.2; 95% CI 2.6-3.9) and non-adhesive bowel obstruction (adjusted OR 2.4; 95% CI 2.0-2.8). The rates of endometriosis among women with or without intussusception were comparable. CONCLUSIONS: Pelvic endometriosis, in particular rectovaginal and intestinal endometriosis is strongly associated with bowel obstruction, independent of the presence of intra-abdominal adhesions. We did not find any association between pelvic endometriosis and intussusception.

A Case Series of Patients with Large Uterine Fibroids and Venous Thromboembolisms.

OBJECTIVE: The purpose of this case series is to identify the clinical characteristics of women with uterine fibroids who developed venous thromboembolisms (VTE) and possible risk factors for the development of VTE in this group. DATA SOURCES: We conducted a systematic search of the Medline, Embase, Cochrane and Scopus databases to retrieve case reports and case series that describe women with an enlarged uterus and VTE. The databases were searched up to August 2019. STUDY SELECTION: A total of 1485 articles were identified by a librarian. All case series and case reports that reported uterine weight and size of the fibroids were included. DATA EXTRACTION AND SYNTHESIS: A total of 27 articles were included, describing 35 patients who developed VTE in the presence of uterine fibroids. On average, the uterus measured 22.9 ± 5.0 weeks gestational age and occupied a volume of 2715 cm3 (interquartile range 1296.3-3878.8) on imaging. Two-thirds (60%) of VTEs occurred on the left side, and 87% showed signs of venous compression on imaging. Most patients (89%) required surgical management to relieve the compression caused by the enlarged uterus. CONCLUSION: VTE in cases of large uterine leiomyomas can be associated with mechanical compression, which requires surgical management to relieve compression. There is an obvious increased risk of VTE in patients with venous stasis secondary to uterine compression; however, there is no current evidence evaluating the use of anticoagulation in such patients. Further research is required to determine the role of prophylactic anticoagulation in reducing the risk of VTE in high-risk patients with large uterine fibroids.

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.

Pregnancy, delivery and neonatal outcomes among women with congenital adrenal hyperplasia: a study of a large US database.

RESEARCH QUESTION: What is the association between congenital adrenal hyperplasia (CAH) and pregnancy, delivery and neonatal outcomes, using a population database cohort. DESIGN: Retrospective study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database from 2004-2014. ICD-9 code 255.2 was used to extract the cases of CAH. Pregnancies complicated with CAH were compared with the other pregnancies. All confounding variables were adjusted using multivariate logistic regression, based on any significant differences between the two groups. RESULTS: A total of 9,096,788 deliveries occurred during the study period. Two hundred and ninety-nine pregnant women had CAH. Chorioamnionitis was higher in CAH compared with controls after controlling for risk factors (adjusted OR 2.67, 95% CI 1.17 to 6.06). The rates of caesarean section and maternal infection were also higher in CAH than controls (adjusted OR 2.10, 95% CI 1.44 to 3.07 and adjusted OR 2.63, 95% CI 1.22 to 5.63, respectively). Risk of gestational diabetes and pregnancy-induced hypertension rates were not significantly different in CAH (adjusted OR 1.53, 95% CI 0.91 to 2.58 and adjusted OR 0.87, 95% CI 0.49 to 1.56, respectively). At birth, 8% and 2.2% of the neonates were found to be small for gestational age in the CAH and the control groups, respectively (adjusted OR 3.37, 95% CI 1.86 to 6.11). Congenital anomalies were encountered in 2.7% and 0.4% in the CAH and control groups, respectively (adjusted OR 5.24, 95% CI 2.31 to 11.90). CONCLUSIONS: Women with CAH were at risk of complications and fetal anomalies. Expected increases in rates of hypertension and gestational diabetes were not encountered. These patients will benefit from surveillance to decrease morbidity.

Trends in ovarian hyperstimulation syndrome hospitalization rates in the USA: an ongoing concern.

Ovarian hyperstimulation syndrome (OHSS) is a serious, almost exclusively, iatrogenic complication of ovarian stimulation. Many techniques have been developed over the past 25 years to decrease OHSS risks, and most have been in common use for 15-20 years. In view of these techniques, it could be hypothesized that severe OHSS rates would decrease or almost disappear. According to the US National ART Surveillance System, rates did not change significantly between 2000 and 2009, at 106 OHSS cases per 10,000 IVF cycles annually. In the present study, OHSS-related hospital admissions were evaluated to establish whether a decline has occurred in OHSS admissions since the development of preventative strategies. A retrospective-population-based study was conducted using data from the Health-Care Cost and Utilization Project-Nationwide-Inpatient-Sample database between 2004 and 2014 inclusively. Between 2004 and 2008, admissions of OHSS decreased in absolute numbers and rates; however, these statistics plateaued, remaining stable between 2008 and 2014. Despite this, OHSS remains a concern and is clearly not a disease of the past. The financial burden of OHSS hospitalizations likely persists. Although techniques have resulted in a decrease in OHSS admissions since 2004, this change has plateaued, and therefore efforts to further reduce OHSS must continue.

Influence of stage and grade of breast cancer on fertility preservation outcome in reproductive-aged women.

RESEARCH QUESTION: Does breast cancer spread and aggressiveness affect fertility-preservation results? DESIGN: Retrospective cohort study of women with breast cancer undergoing fertility-preservation treatment. INCLUSION CRITERIA: age 18-38 years and use of gonadotrophin releasing hormone antagonist protocol; exclusion criteria: recurrent cancer, previous oncological treatment, previous ovarian surgery and known ovarian pathology. Stimulation cycle outcomes of women with low-stage breast cancer were compared with those with high-stage disease. Patients with low-grade (G1-2) were compared with those with high-grade (G3) malignancies. PRIMARY OUTCOME: total number of mature oocytes; secondary outcomes: oestradiol level and number of follicles wider than 14 mm on the day of trigger, number of retrieved oocytes and cryopreserved embryos. RESULTS: The final analysis included 155 patients. Patients with high-grade tumours (n = 80; age 32 years [28-35]) had significantly lower number of mature oocytes compared with patients with low-grade cancer (n = 75; age 32 years [28-35]; seven mature oocytes [4-10] versus 13 mature oocytes [7-17]; P = 0.0002). The number of cryopreserved embryos was also lower in the high-grade group (three [2-5] versus five [3-9]; P = 0.02). Stage-based analysis revealed a similar number of mature oocytes in high-stage (n = 73; age 32 years [28-35]) compared with low-stage group (n = 82; age 33 years [28-35]; eight mature oocytes [4-13] versus nine mature oocytes [7-15]; P = 0.06). CONCLUSIONS: High-grade breast cancer has a negative effect on total number of mature oocytes and cryopreserved embryos.

Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response.

STUDY QUESTION: Do the stage and grade of malignancy affect the fertility preservation outcome in females? SUMMARY ANSWER: Patients with high-grade cancer have a decreased number of retrieved mature oocytes and cryopreserved embryos. WHAT IS KNOWN ALREADY: Cancer has local and systemic effects on the host. The effects of cancer spread and aggressiveness on the ovarian function and stimulation response remain unclear. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study evaluating data of all fertility preservation treatment cycles among women with cancer at the reproductive unit of the McGill University Health Centre in the period from 2008 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study inclusion criteria were age 18-38 years, first stimulation cycle, GnRH-antagonist protocol and early follicular phase stimulation start. Only one stimulation cycle per patient was included. Patients with ovarian pathology, previous ovarian surgery and previous chemo- or radiotherapy were excluded. The outcomes of women with low-stage cancer (local tumor Stage I-II, no lymph node involvement, no metastases) were compared with those with high-stage disease (local tumor Stage III-IV, lymph node involvement or metastases). Similarly we compared those with low-grade (G1-2) and high-grade (G3-4) malignancies. The primary outcome measure was the number of mature oocytes retrieved. The secondary outcomes included the total number of retrieved oocytes, the number of vitrified oocytes, and the number of frozen embryos. We used Student's t-test for normally distributed data and Wilcoxon test for skewed data. To determine factors associated with good fertility preservation outcome defined as over 10 retrieved mature oocytes, we used multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 147 patients were included in the final analysis. Age, body mass index, ovarian reserve parameters of the study groups in stage- and grade-based analyses were similar. Compared to women with low-stage cancer (n = 83), those with high-stage cancer (n = 64) required a higher dose of gonadotropin (P = 0.02). The number of retrieved mature oocytes (9 (7-13) versus 8 (5-12); P = 0.37) and vitrified oocytes (10 (7-15) versus 10 (7-13); P = 0.53) were similar between the two groups. However, in cycles where fertilization of all retrieved oocytes was performed, the fertilization rate (82.7% versus 71.5%; P = 0.03) and the number of vitrified embryos (6.2 ± 3.2 versus 4.3 ± 2.1; P = 0.01) were higher in the low-stage group. Compared to patients with low-grade cancer (n = 62), those with high-grade disease (n = 85) had significantly lower number of retrieved mature oocytes (11 (7-15) versus 8 (5-11); P = 0.002) and vitrified oocytes (12 (8-15) versus 10 (7-11); P = 0.005). The number of vitrified embryos was lower in high-grade group (6.5 ± 3.5 versus 4.6 ± 2.3; P = 0.03) in cycles where the fertilization was performed. In multivariate logistical analysis, the low-grade cancer was significantly associated with retrieval of over 10 mature oocytes (OR = 4.26; 95% CI 1.82-9.98; P = 0.0009). LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study include its retrospective design and the relatively small sample size in the embryological outcome analysis. The results of our study should be viewed with caution as different malignancy types were included in the study groups, although their distribution between the study groups was similar. WIDER IMPLICATIONS OF THE FINDINGS: Cancer grade seems to have a negative impact on the fertility preservation outcome and the ovarian stimulation response. STUDY FUNDING/COMPETING INTEREST(S): Authors have not received any funding to support this study. There are no conflicts of interest to declare.