Fertility preservation parameters in patients with haematologic malignancy: a systematic review and meta-analysis.

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis. Despite a younger age (mean difference -4.17, 95% CI -6.20 to -2.14; P < 0.0001), patients with haematologic malignancy had lower serum anti-Müllerian hormone levels compared with the control group (MD -1.04, 95% CI -1.80 to -0.29; P = 0.007). The marginally higher total recombinant FSH dose (MD 632.32, 95% CI -187.60 to 1452.24; P = 0.13) and significantly lower peak oestradiol serum level (MD -994.05, 95% CI -1962.09 to -26.02; P = 0.04) were demonstrated in the study group compared with the healthy controls. A similar number of retrieved oocytes were achieved in both groups (MD 0.20, 95% CI -0.80 to 1.20; P = 0.69). In conclusion, haematologic malignancies may detrimentally affect ovarian function manifesting in decreased AMH serum levels despite a younger age compared with healthy controls. This effect can be overcome by the application of relevant IVF protocols and stimulation doses to achieve an adequate oocyte yield.

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach.

Background: Understanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease. Methods: To obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques. Results: We analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn's disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment. Conclusion: Our findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.

Combined Hormonal Contraception during Breastfeeding-A Survey of Physician's Recommendations.

Until breastfeeding is established, progesterone-only pill (POP) use is preferable over combined hormonal contraception (CHC), as the latter potentially reduces milk production. Yet, POPs are often associated with breakthrough bleeding (BTB), and irregular spotting is often a reason for their cessation. Conversely, CHC is less associated with BTB but is not usually prescribed, even if breastfeeding has been established, despite its verified safety profile. Here, we surveyed physicians' perception of CHC safety during breastfeeding through an online questionnaire (N = 112). Physicians were asked if they would prescribe CHC to a woman three months postpartum, breastfeeding fully, and suffering from BTB while using POPs. Half of the physicians responded they would, 28% would not until six months postpartum, while 14% would not during breastfeeding. Of the physicians that would prescribe CHC, 58% would without any reservation, 24% would only after discussing milk reduction with the patient, 9% would use a pill with a lower hormonal dose, and 9% would only prescribe CHC 3 months postpartum. The main risk associated with CHC during breastfeeding, as perceived by physicians, is a potential decrease in breast milk production (88%). While some physicians consider CHC unsafe during breastfeeding, most health organizations consider CHC compatible with breastfeeding 5-6 weeks after birth. Thus, there is a gap in the attitude and knowledge of physicians about the safety profile of CHC, and only half acknowledge that the risk of BTB justifies the use of CHC instead of POPs while breastfeeding three months postpartum. We highlight the importance of physician's education, advocate CHC breastfeeding compatibility if breastfeeding has been established (i.e., 30 days postpartum), and underline the importance of discussing the option of CHC with patients in case POPs have unwanted side effects.

Effect of Malignancy on Semen Parameters.

Purpose: We aimed to examine how various types of cancer, classified histologically, affect semen quality. Methods: The study group included 313 patients who were diagnosed with cancer and reached for a sperm cryopreservation before a gonadotoxic treatment (PG-Tx group). Their semen parameters were compared to those of two control groups: (a) individuals who attended a fertility investigation and were found to be above the limit of the lower reference value of the WHO 2010 manual (ARL group), and (b) fertile men, whose semen parameters were obtained from the dataset of the WHO 2020 manual. Results: Semen quality was significantly poorer in the PG-Tx group than in the ARL group. Differences included a 65.6% decrease in concentration, a 12.1% decrease in volume, a 72.7% decrease in total count, and a 33.0%, 22.2%, and 24.7% decrease in total motility, rapid motility, and progressive motility, respectively. Linear regression models comparing the PG-Tx and ARL groups revealed that the maximum reduction in total motility and concentration was in men with germ-cell tumors, whereas the minimum reduction was in hematological tumors. Similarly, all sperm quality parameters were significantly lower in the PG-Tx group than in the fertile-men group (p < 0.0001). Conclusions: While the effect of malignancy on semen parameters is debatable, we found that all examined types of cancer significantly impaired sperm quality parameters. Although the median of most semen parameters of patients with cancer were still in the normal WHO range, their fifth percentile, represents men with a delayed time to pregnancy.

Geographic variation in semen parameters from data used for the World Health Organization semen analysis reference ranges.

OBJECTIVE: To study geographic variations in sperm parameters using data from the trials that defined the reference ranges of the World Health Organization 2021 manual. DESIGN: Retrospective evaluation of the data used to define the World Health Organization reference ranges. SETTING: Not applicable. PATIENT(S): Data from 11 studies, including 3,484 participants across 5 continents. INTERVENTION(S): The data were divided according to geographic locations. MAIN OUTCOME MEASURE(S): Differences in sperm parameters. RESULT(S): The semen volume was significantly lower in samples from Asia and Africa than in other regions. The sperm concentration was the lowest in Africa and highest in Australia. The total motile sperm count (TMSC) and total motile progressive sperm count (TMPS) were significantly lower in Africa than in other regions. The TMSC and TMPS in Asia and the United States were significantly lower than in Europe and Australia. The 5th percentile of the sperm concentration was lowest in the United States (12.5 × 106/mL). The 5th percentile for the normal sperm morphology was lowest in the United States (3%) and highest in Asia (5%). The 5th percentile for the TMSC and TMPS were lowest in Africa (TMSC, 15.08 million; TMPS, 12.06 million) and the United States (TMSC, 18.05 million; TMPS, 16.86 million) and highest in Australia (TMSC, 29.61 million; TMPS, 25.80 million). CONCLUSION(S): Significant geographic differences in sperm parameters exist, and regional fertility societies should consider adding their own reference ranges on the basis of local experience and treatment outcomes.

An evaluation of changes over time in the semen parameters data used for the World Health Organization semen analysis reference ranges.

BACKGROUND: Previous meta-analyses concluded that there is a decline in sperm parameters over time. This conclusion might be incorrect due to inherent biases or focusing only on a single parameter - sperm concentration. OBJECTIVE: To study trends in sperm parameters over the past 20 years using data from the trials that defined the reference ranges of the World Health Organization manual. MATERIALS AND METHODS: Retrospective evaluation of the data used to define the World Health Organization reference ranges. The data from 11 studies, including 3589 participants between 1996 and 2016, were divided into three period groups based on the decade of study. Differences in semen parameters' distribution were presented in boxplot. p-values were calculated by the Kruskal-Wallis rank-sum test followed by Dunn post hoc test. Analyses were conducted using the R programming language. RESULTS: A small decrease was noted in mean sperm concentrations (88.1 million/ml, 87.6 million/ml, and 77.2 million/ml for the first, second, and third decades, respectively) (p < 0.01). However, the 5th percentile of sperm concentration for the third decade was higher than the first or second decades (18 million/ml versus 14.9 million/ml and 15 million/ml, respectively). No significant differences were noted in progressive motility over the years (p = 0.32). The percent of morphologically normal sperm decreased between the first (24.2%) and the second (12.6%) periods of the study (p < 0.001) and then increased in the third decade (14.2%) (p < 0.01). Total motile sperm count (TMC) declined between the second and third decades (189 million and 153.9 million, respectively, p < 0.001), at levels unlikely to decrease fertility. However, the 5th percentile of the TMC remained stable at 24.9, 20.8, and 20.6 million, for the first, second, and third decades respectively (p = 0.36). DISCUSSION AND CONCLUSION AND RELEVANCE: Trends in sperm parameters over the last three decades do not seem to be clinically significant.

Influence of Maternal Age and Ovarian Reserve on the Decision to Continue or to Cancel IVF Cycles in Patients with One or Two Large Follicles: a Dual Effect.

This study aimed to study whether IVF stimulation that results in one or two mature follicles should proceed to oocyte retrieval. This is a retrospective cohort study conducted at McGill University Health Center on 459 patients who underwent IVF treatment between 2011 and 2014, undergoing hormonal stimulation and monitoring of their ovarian response. The primary outcomes were pregnancy and live birth rates. Statistical modeling was used to determine individual roles of patient age and ovarian reserve on outcomes, while controlling for the other factors. Of the 459 cycles included in the study, 360 cycles (78.4%) ended in embryo transfer. Live birth rates per cycle were 15.6%, for the ≤ 34-year-olds; 6.5%, for the 35-39-year-olds; and 2.7%, for the ≥ 40-year-olds (p < 0.01). Twenty-five percent of the cycles in the ≥ 40-year-old group were canceled versus 17% and 15% in the 35-39-year-old and ≤ 34-year-old groups, respectively (p < 0.05). Testing likelihood of live birth as a function of age and antral follicular count (AFC) revealed that a 1-year increase in age reduces the likelihood of live birth by 11% (p < 0.05) and one-unit increase in AFC count leads to a 9% increase in the odds of a live birth (p < 0.05). For the youngest age group, the AFC had a most significant effect, and those with AFC > 11 had 56% live birth rate, while those with AFC ≤ 11 had only 6% of live birth rate. This study supports a shift in reasoning from age being the predictor of outcomes in women with a low response at IVF to both age and ovarian reserve needing to be taken into consideration.

Hope for male fecundity: clinically insignificant changes in semen parameters over 10 years at a single clinic while assessing an infertility population.

PURPOSE: What is the trend in sperm parameters in a group of men attending a single reproductive center, over a 10-year period? METHODS: A retrospective study was conducted on 12,188 semen samples obtained from unique individuals who attended a university reproductive clinic from 2009 to 2018, inclusively. Semen analysis was done using computer-assisted sperm analysis and verified by an andrologist. Analysis was done after dividing the dataset into two groups: above WHO 2010 lower reference limits (ARL) (N = 6325) and below the reference limits (BRL) (N = 5521). RESULTS: Volume increased slightly (ARL, p = 0.049) before returning to baseline or was stable (BRL, p = 0.59). Sperm concentration and total count of the BRL and ARL group declined initially and then recovered slightly (p < 0.0001, in all cases). Although these changes were statistically significant, this was due to the large study population; clinically, these changes were quite mild and would not have been significant for fertility. Sperm total motility and progressive motility of both the BRL group and the ARL group increased slightly from 2009 until 2015 and then decreased back to baseline (p < 0.0001). This change offset the decrease in count seen in those years. A spurious change was observed with sperm morphology that declined after the first 2 years and remained stable thereafter (p < 0.0001, in both groups). However, this change was attributed to a contemporaneous change in the method of analyzing strict morphology which happened when the change occurred. CONCLUSION: While statistically significant changes were found, clinically, these changes were quite mild and would not have been significant for fertility.

An age-based sperm nomogram: the McGill reference guide.

STUDY QUESTION: How does age affect various semen parameters? SUMMARY ANSWER: For most semen parameters, the nomogram of the entire population was biphasic, peaking around the fourth decade of life. WHAT IS KNOWN ALREADY: In clinical practice, semen quality is examined by using the WHO 2010 reference limits but these limits do not account for male age. A percentile-based, large-scale nomogram describing how different semen parameters change throughout reproductive life has been lacking. STUDY DESIGN, SIZE, DURATION: A retrospective study was conducted with 12 188 sperm samples, obtained from individuals who attended the McGill University Health Centre reproductive clinic between 2009 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: One sample from each individual who attended the clinic during the study period was analysed by using computer-assisted sperm analysis (CASA). The analysed parameters were human-verified and included sperm concentration, motility, progressive motility, total count, morphology and semen volume. Based on this analysis, the entire dataset (n = 12 188) was further divided into two groups of samples: samples that surpassed the WHO 2010 lower reference limits ('above reference limits' group, ARL; n = 6305), and samples that did not ('below reference limit' group, BRL; n = 5883). Regression quantiles were fitted as a function of age to generate age-dependent nomograms, and these quantiles were divided into 5th, 25th, 50th, 75th and 95th percentiles. MAIN RESULTS AND THE ROLE OF CHANCE: In the entire dataset, age had a significant influence (P < 0.001) on all parameters (except morphology) which demonstrated a biphasic trend peaking in the fourth decade of life. In the ARL group, age had a significant influence (P < 0.01) on all semen parameters except sperm concentration and morphology. However, unlike in the entire dataset, only semen volume demonstrated a biphasic trend in the ARL group (peaking in the fourth decade of life), whereas other parameters either remained unchanged (concentration and morphology) or consistently declined with age (sperm motility, progressive motility and total sperm count). Percentile-based nomograms were generated for individuals between the ages of 20 and 60 years in the entire dataset and in the ARL group. LIMITATIONS, REASONS FOR CAUTION: First, the semen samples were obtained from individuals who were referred to a fertility clinic, such that the entire dataset does not necessarily represent the general population. Second, the cross-sectional sampling design increases variance, and the nomograms are less accurate in the 5th and 95th percentiles and at the extremes of the age distributions. Third, the observed age-dependent changes in semen parameters do not necessarily indicate changes in fertility, as not all factors that affect male fertility were analysed. Fourth, some of our semen analyses employed CASA, which can have variability issues. Finally, our models did not incorporate possible secular trends. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first nomogram that correlates age with semen quality parameters in different population percentiles, thus complementing the current reference limits set by the WHO in 2010. Most examined semen parameters in our study changed non-linearly with age; therefore, age should be regularly employed as a factor in the clinical analysis of semen samples. STUDY FUNDING/COMPETING INTEREST(S): The authors have not received any funding to support this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

A comparison of IVF outcomes transferring a single ideal blastocyst in women with polycystic ovary syndrome and normal ovulatory controls.

PURPOSE: To assess the effects PCOS on live birth rates when transferring a single fresh ideal blastocyst. METHODS: A retrospective cohort study performed at the university-affiliated reproductive center. Women with PCOS and a control group of normal ovulatory women who underwent their first fresh embryo transfer with single ideal grade blastocyst were included in the study. Demographic, stimulation information and pregnancy outcomes were collected and analysed. The primary outcome was live birth rates, and secondary outcomes included pregnancy and clinical pregnancy rates. RESULTS: 71 Women with PCOS and 272 normal ovulatory controls underwent their first embryo transfer and met the inclusion and exclusion criteria. PCOS patient were younger (31.0 ± 3.7 vs. 33.1 ± 3.2, p = 0.0001), with higher AFC (40.0 ± 9.3 vs. 13.3 ± 4.6, p = 0.0001), required lower dose of gonadotropins to stimulate (1198 ± 786 vs. 1891 ± 1224, p = 0.0001), and had higher serum testosterone levels (2.3 ± 0.7 vs. 1.1 ± 0.3, p = 0.0001). No significant difference was found between the two groups regarding the number of previous pregnancies, the number of previous full-term pregnancies, the level of basal serum FSH, estradiol level at triggering and the BMI. When compared by Chi squared testing pregnancy rates, clinical pregnancy rates and live birth rates did not differ. However, when controlling (with multivariate stepwise logistic regression) for confounders, live birth rates were lower among the women with PCOS (p = 0.035, CI: 0.18-0.92). CONCLUSION: After controlling for confounders, when transferring a fresh single ideal blastocyst, live birth rates were lower among the women with PCOS than normal ovulatory controls.

Outcomes of ovarian stimulation and fertility preservation in breast cancer patients with different hormonal receptor profiles.

PURPOSE: To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment. METHODS: The study population included women with a diagnosis of breast cancer who underwent fertility preservation from 2009 until 2018 at a university-affiliated tertiary hospital. Stimulation parameters and fertility preservation outcomes were compared among the following receptor-specific profile groups: (1) estrogen receptor positive (ER+) versus estrogen receptor negative (ER-), (2) triple-negative breast cancer (TNBC) versus estrogen and progesterone receptor positive (ER+/PR+), and (3) TNBC versus non-TNBC. Primary outcome was the total number of mature oocytes. Secondary outcomes included the number of retrieved oocytes, the peak estradiol level, and the number of follicles > 14 mm on the final oocyte maturation trigger day. RESULTS: A total of 155 cycles were included in the final analysis. These were divided into the exposure groups of ER+ (n = 97), ER- (n = 58), ER+/PR+ (n = 85), TNBC (n = 57), and non-TNBC (n = 98). Cycle outcomes revealed similar number of retrieved oocytes and follicles > 14 mm on the trigger day. Women with TNBC had significantly lower number of mature oocytes compared with those with ER + PR+ (7 (5-11) versus 9 (7-15); p = 0.02) and non-TNBC (7 (5-11) versus 9 (7-16); p = 0.01) status. Triple-negative breast cancer profile was associated with a significant reduction in the chance of developing over 10 mature oocytes (OR 0.41; 95% CI 0.19-0.92). CONCLUSION: Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.

Solving the Obstetrical Paradox: The FETAL Technique-A Step toward Noninvasive Evaluation of Fetal pH.

Every year, about 85 percent of the approximately 5 million births in North America are evaluated with the electronic fetal monitoring (EFM). Clinicians use the EFM as a proxy to assess fetal oxygenation status, fetal well-being, and potential compromise. Despite the widespread use of this technology, neonatal hypoxia and acidosis continue to make up a high proportion of neonatal morbidity at term. Indeed, though the fetal heart rhythm is inextricably linked to fetal acid-base status, EFM has not been shown to reliably predict neonatal pH status nor has it reduced adverse maternal or neonatal outcomes. As a consequence, the high false-positive rate of EFM for predicting adverse neonatal outcomes has led to an increase in the rate of operative vaginal and cesarean delivery, with elevated rates of associated maternal and neonatal morbidity. This fact invariably leads to a paradox we have henceforth defined as the "obstetrical paradox." Herein, we explore the potential solutions to this paradox and introduce a novel noninvasive technique to assess fetal acid-base status in utero known as the "FETAL technique" (Fourier Evaluation of Tracings and Acidosis in Labour). The FETAL technique, currently under investigation, applies the discrete Fourier transformation to EFM tracings to determine the spectral frequency distribution of the fetal heart rate. These specific frequency distributions correlate with specific umbilical pH values and may provide the missing link between fetal heat rate patterns and acid-base status at birth. As we work toward realizing the full potential benefits of EFM, finding the best assessment strategies to evaluate fetal pH in real time remains a key goal in obstetrics.

Chronic Endometritis in Fertile and Infertile Women Who Underwent Hysteroscopic Polypectomy.

STUDY OBJECTIVE: To evaluate the prevalence of chronic endometritis (CE) among fertile and infertile women who underwent hysteroscopic polypectomy. DESIGN: A retrospective cohort study. SETTING: University-affiliated tertiary hospital. PATIENTS: A total of 277 women who underwent hysteroscopic polypectomy in the period from 2015 to 2018. INTERVENTIONS: Endometrial polyp samples were obtained after hysteroscopy for histopathologic analysis using hematoxylin-eosin and immunohistochemistry staining with CD138 antibodies for plasma cell detection. All infertile women diagnosed with CE were treated with oral doxycycline 100 mg twice daily for 14 days before infertility treatment. MEASUREMENTS AND MAIN RESULTS: The prevalence of CE in infertile women (n = 137) was significantly higher than in those with no history of infertility (n = 140) (22.6% vs 8.6%; p = .001). The prevalence of CE between women with primary infertility and those with secondary infertility was similar (25.0% vs 19.3%; p = .43). Clinical pregnancy (32.3% vs 41.5%; p = .35), live birth (29.0% vs 38.7%; p = .33), and miscarriage (10.0% vs 6.8%; p = .73) rates were similar between infertile women with treated CE and those without CE. A multivariate model showed that diagnosis of infertility was significantly associated with the diagnosis of CE (odds ratio, 3.16; 95% confidence interval, 1.53-6.49). CONCLUSION: In women with endometrial polyps, the prevalence of CE in infertile women is higher than that in fertile women. Pregnancy outcome in infertile women with treated CE was similar to those who were infertile and without CE.

Placenta previa and the risk of intrauterine growth restriction (IUGR): a systematic review and meta-analysis.

Background Whether placental location confers specific neonatal risks is controversial. In particular, whether placenta previa is associated with intra-uterine growth restriction (IUGR)/small for gestational age (SGA) remains a matter of debate. Methods We searched Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science and Cochrane database search, as well as PubMed (www.pubmed.gov) until the end of December 2018 to conduct a systematic review and meta-analysis to determine the risk of IUGR/SGA in cases of placenta previa. We defined IUGR/SGA as birth weight below the 10th percentile, regardless of the terminology used in individual studies. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. We used odds ratios (OR) and a fixed effects (FE) model to calculate weighted estimates in a forest plot. Statistical homogeneity was checked with the I2 statistic using Review Manager 5.3.5 (The Cochrane Collaboration, 2014). Results We obtained 357 records, of which 13 met the inclusion criteria. All study designs were retrospective in nature, and included 11 cohort and two case-control studies. A total of 1,593,226 singleton pregnancies were included, of which 10,575 had a placenta previa. The incidence of growth abnormalities was 8.7/100 births in cases of placenta previa vs. 5.8/100 births among controls. Relative to cases with alternative placental location, pregnancies with placenta previa were associated with a mild increase in the risk of IUGR/SGA, with a pooled OR [95% confidence interval (CI)] of 1.19 (1.10-1.27). Statistical heterogeneity was high with an I2 = 94%. Conclusion Neonates from pregnancies with placenta previa have a mild increase in the risk of IUGR/SGA.

Use of cabergoline and post-collection GnRH antagonist administration for prevention of ovarian hyperstimulation syndrome.

RESEARCH QUESTION: Does the addition of a gonadotrophin-releasing hormone (GnRH) antagonist to cabergoline treatment during the luteal phase in fresh IVF cycles triggered with a GnRH agonist, and planned for freeze-all, reduce the rate of mild and moderate ovarian hyperstimulation syndrome (OHSS)? DESIGN: Retrospective cohort study of 480 IVF patients at risk for OHSS with GnRH agonist trigger from 2011 to 2018, stratified into three groups based on treatment received: GnRH agonist trigger alone (Group 1, n = 208), GnRH agonist trigger + cabergoline (Group 2, n = 167) or GnRH agonist trigger + cabergoline + GnRH antagonist (Group 3, n = 105). Data on patient demographics, incidence, severity and symptomatology of OHSS and laboratory findings were collected. RESULTS: Group 1 had more free peritoneal fluid than Group 2 (28% versus 19%, P = 0.04) or Group 3 (28% versus 5%, P = 0.001). Group 1 reported abdominal discomfort and bloating more than Group 2 (33% versus 21%, P = 0.01) or Group 3 (33% versus 18%, P = 0.006). Group 1 had more electrolyte abnormalities than Group 2, who had more than Group 3. No patients developed severe OHSS. Mild and moderate OHSS rate was higher in Group 1 (38%) than Group 2 (29%, P = 0.048) or Group 3 (18%, P = 0.006) and in Group 2 than Group 3 (P = 0.046). CONCLUSION: Addition of cabergoline to GnRH agonist triggering in high-risk OHSS patients, and subsequent addition of GnRH antagonist for 5 days in the luteal phase, sequentially reduces the risk of mild and moderate OHSS and improves patient comfort compared with GnRH agonist trigger alone.

Amount of Progesterone Consumed Based on Varying Fat Concentrations, Dietary Recommendations, and Estimated Safe Levels in Commercial Cow Origin Liquid Dairy Products.

Federal guidelines recommend that food with hormone content fall below 1% of endogenous production in the subset of the population with the lowest daily production. The majority of dairy products are obtained from pregnant cows, which increase the level of hormones present. The purpose of this article was to perform theoretical evaluation of the quantity of progesterone in cow's milk based on fat percentages and to assess whether this was within the recommended range. Daily recommended dairy product intake from various countries worldwide was researched. This was compared to the concentration of progesterone previously identified in varying fat contents of cow origin milk to assess the amount of progesterone (mg/day) that would be consumed if the guidelines were followed. The maximum daily progesterone consumption suggested will be met by ingestion of 2.7 L, 1.42 L, 1.13 L, 940 mL, 810 mL, 650 mL of 0% (skim), 1%, 2%, 3.25%, 10% (cream), and 35% (whipping cream) fat liquid cow origin dairy product, respectively. Therefore, ingestion of the highest amount of recommended daily dairy intake fell below 1% of the daily endogenous quantity produced, except in the unlikely case of consumption of 650 mL of 35% fat. Studies demonstrating an effect of cow's liquid dairy product intake may need to be revisited, since levels of progesterone consumption remain within the recommended levels. However, it should be considered that ingestion of cow's milk might have a potential effect on the hormonal profile in patients; however, this seems unlikely.

Effect of GnRH agonist and letrozole treatment in women with recurrent implantation failure.

OBJECTIVE: To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). DESIGN: Retrospective cohort study. SETTING: University-affiliated reproductive center. PATIENT(S): A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. INTERVENTION(S): A total of 204 subjects were not pretreated, 143 received 2 months of GnRH agonist (3.75 mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5 mg oral letrozole daily for 60 days). Demographic and stimulation information was collected and cycle outcomes reported. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P<.0001). Live birth rates were higher among women who received GnRH agonist plus letrozole compared with the other groups (56%, 36%, and 34%; P<.0001). No differences in pregnancy outcomes were noted between patients who did not receive pretreatment and those in the GnRH agonist only group. CONCLUSION(S): In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis.

Use of artificial intelligence (AI) in the interpretation of intrapartum fetal heart rate (FHR) tracings: a systematic review and meta-analysis.

OBJECTIVES: To determine the degree of inter-rater reliability (IRR) between human and artificial intelligence (AI) interpretation of fetal heart rate tracings (FHR), and to determine whether AI-assisted electronic fetal monitoring interpretation improves neonatal outcomes amongst laboring women. DATA SOURCES: We searched Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science and Cochrane database search, as well as PubMed ( www.pubmed.gov ) and RCT registry ( www.clinicaltrials.gov ) until the end of October 2018 to conduct a systematic review and meta-analysis comparing visual and AI interpretation of EFM in labor. Similarly, we sought out all studies evaluating the IRR between AI and expert interpretation of EFM. TABULATION, INTEGRATION AND RESULTS: Weighed mean Cohen's Kappa was calculated to assess the global IRR. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. We used relative risks (RR) and a random effects (RE) model to calculate weighted estimates. Statistical homogeneity was checked by the χ2 test and I2 using Review Manager 5.3.5 (The Cochrane Collaboration, 2014.) We obtained 201 records, of which 9 met inclusion criteria. Three RCT's were used to compare the neonatal outcomes and 6 cohort studies were used to establish the degree of IRR between both approaches of EFM evaluation. With regards to the neonatal outcomes, a total of 55,064 patients were included in the analysis. Relative to the use of clinical (visual) evaluation of the FHR, the use of AI did not change the incidence rates of neonatal acidosis, cord pH below < 7.20, 5-min APGAR scores < 7, mode of delivery, NICU admission, neonatal seizures, or perinatal death. With regards to the degrees of inter-rater reliability, a weighed mean Cohen's Kappa of 0.49 [0.32-0.66] indicates moderate agreement between expert observers and computerized systems. CONCLUSION: The use of AI and computer analysis for the interpretation of EFM during labor does not improve neonatal outcomes. Inter-rater reliability between experts and computer systems is moderate at best. Future studies should aim at further elucidating these findings.

The influence of obesity, smoking, and serum follicular stimulating hormone in azoospermic patients on testicular sperm extraction-intra cytoplasmic sperm injection outcomes: A retrospective cohort study.

To examine the effect of serum follicle-stimulating hormone (sFSH) level, body-mass index (BMI) and smoking on Testicular Sperm Extraction-Intracytoplasmic Sperm Injection (TESE-ICSI), and pregnancy outcomes.In this retrospective study, data were extracted from files of 52 azoospermic men who underwent TESE and in-vitro fertilization (IVF)-ICSI in our IVF unit. Demographic information, treatment cycle follow-up and pregnancy outcomes were collected.Fifty-two patients underwent 79 TESE due to azoospermia in 143 IVF cycles. Smoking was found to significantly affect sperm motility in TESE specimens before freezing (45.5% vs 14.8%; P <.001); however, this finding did not influence the pregnancy rate. Male FSH was inversely correlated with testicle volume (r = -0.595, P <.0001). Body weight did not affect semen parameters after TESE or ICSI outcomes.Among azoospermic patients with extremely poor sperm quality, male BMI, male FSH or smoking did not have an adverse effect sperm parameters or pregnancy and delivery rates.