Publications by authors named "Michael H Dahan"

131 Publications

Association between obesity in women with polycystic ovary syndrome and adverse obstetric outcomes.

Reprod Biomed Online 2022 Feb 15. Epub 2022 Feb 15.

McGill University, McGill University Health Center, Reproductive Center, Department of Obstetrics and Gynecology, MUHC Reproductive center, McGill University, 888, Boulevard de Maisonneuve East, Suite 200, Montreal QC H2L 4S8, Canada. Electronic address:

Research Question: How does the presence of obesity modify the risks for adverse obstetric outcomes in women with polycystic ovary syndrome (PCOS)?

Design: Retrospective population-based cohort study using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample, 2004-2014. A total of 14,855 women with PCOS were identified (study group: obese women with PCOS [BMI ≥30 kg/m] [n = 3286]; reference group: remaining women with PCOS [n =11 569]). Logistic regression analysis was used to explore the associations between obesity, pregnancy, delivery and neonatal outcomes.

Results: Obesity was associated with a higher prevalence of chronic hypertension (P < 0.001), pregestational diabetes (P < 0.001) and a previous caesarean delivery (P < 0.001). Obesity increased the risk of gestational diabetes (adjusted [a]OR 1.745; 95% CI 1.473 to 2.067), pregnancy-induced hypertension (aOR1.889; 95% CI 1.589 to 2.246), gestational hypertension (aOR 1.555; 95% CI 1.219 to 1.983) and preeclampsia (aOR 2.170; 95% CI 1.683 to 2.798). Maternal obesity in PCOS increased the risk of chorioamnionitis (aOR 1.548; 95% CI 1.072 to 2.235) and caesarean delivery (aOR 1.414; 95% CI 1.210 to 1.653) and decreased the likelihood of a spontaneous vaginal delivery (aOR 0.751; 95% CI 0.644 to 0.876). Infants born to obese mothers with PCOS were not more likely to be SGA (aOR 0.775; 95% CI 0.511 to 1.175) or to have congenital anomalies (aOR 0.849; 95% CI 0.483 to 1.490).

Conclusion: In women with PCOS, obesity increases the risk of specific pregnancy and delivery complications.
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http://dx.doi.org/10.1016/j.rbmo.2022.02.007DOI Listing
February 2022

Should pregnant women with diabetes be counseled differently if nephropathy was detected? a population database study.

J Matern Fetal Neonatal Med 2022 Mar 25:1-8. Epub 2022 Mar 25.

Department of Obstetrics and Gynecology, McGill University, Montreal, Canada.

Introduction: The prevalence of diabetes mellitus has increased tremendously in the last two decades among women of reproductive age and this is mainly due to the pandemic of obesity. Diabetes mellitus is a well-known cause of maternal and neonatal complications in pregnancy. Diabetic nephropathy is a marker of severe diabetes and results in organ damage. However, only a small number of studies have evaluated the implications of diabetic nephropathy on pregnancy complications, with most having 50 to 100 nephropathy subjects. Our study aims to compare pregnant women with diabetes mellitus complicated by nephropathy or not and evaluate the relationship with obstetrical and perinatal morbidity and mortality, on a larger population.

Methods: This was a population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) including women who delivered between 2004 and 2014. Multivariate logistic regression was used to control for confounding effects.

Results: Among 86,615 pregnancies that were complicated by diabetes mellitus, 1,241 (1.4%) had diabetic nephropathy. Diabetic nephropathy was strongly associated with preeclampsia (aOR 2.3, 95% CI 1.90-2.68), as well as chronic hypertension with superimposed preeclampsia or eclampsia (aOR 4.2, 95% CI 3.53-5.01), preterm birth (aOR 1.8, 95% CI 1.59-2.1), and blood transfusion (aOR 3.6 95% CI 2.82-4.46). Both groups were similar in age and income.

Conclusion: Diabetic nephropathy is associated with increased obstetrical and perinatal morbidity compared to diabetes mellitus alone. These patients may benefit from a high dose of folic acid, more vigilant antenatal surveillance, delivery in a tertiary care center, and more rigorous screening and prevention methods for pregnancy-induced hypertension diseases at antenatal care visits.
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http://dx.doi.org/10.1080/14767058.2022.2049749DOI Listing
March 2022

Placental histology and pregnancy complications following intracytoplasmic sperm injection for non-male factor infertility.

J Assist Reprod Genet 2022 May 21;39(5):1135-1141. Epub 2022 Mar 21.

Department of Obstetrics and Gynecology, McGill University, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.

Purpose: To assess obstetric outcomes and placental histology following intracytoplasmic sperm injection (ICSI), for non-male infertility.

Methods: This was a retrospective cohort of live born singleton deliveries after in vitro fertilization (IVF) at a single university affiliated medical center between 2009 and 2017. Excluded were IVF cycles with male infertility and oocyte recipients. We compared obstetric outcomes and placental histology in cases ICSI was performed (ICSI group) and cases with no ICSI (IVF group).

Results: A total of 400 deliveries following ICSI were compared to 218 in the IVF group. Maternal age was similar between the groups, while diminished ovarian reserve was more common among ICSI patients and tubal disease less common (p < 0.001). The rate of blastocyte transfer was also significantly lower in the ICSI group-67.5% vs. 77%, p = 0.01. Pregnancies following ICSI were characterized by similar rates of preeclampsia, preterm birth, and small for gestational age neonates. Although cesarean delivery rate was significantly higher in the group, this did no attain significance after adjustment for confounders. Placentas in the ICSI group were notable for a lower rate of villitis of unknown etiology (1% vs. 4.5%, p = 0.007) and a higher rate of maternal surface calcifications (33% vs. 23.8%, p = 0.01) after adjustment for confounders.

Conclusion: The employment of ICSI with no male indication is associated with similar obstetric outcomes. Despite isolated placental differences among many investigated, placental histology seems overall comparable as well. These results are reassuring to clinicians and patients.
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http://dx.doi.org/10.1007/s10815-022-02404-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107542PMC
May 2022

Associations between hyperthyroidism and adverse obstetric and neonatal outcomes: A study of a population database including almost 17,000 women with hyperthyroidism.

Clin Endocrinol (Oxf) 2022 Mar 9. Epub 2022 Mar 9.

Department of Obstetrics and Gynecology, Mcgill University, Montreal, Québec, Canada.

Objective: Large population-based studies on maternal hyperthyroidism's effect on antepartum, intrapartum, and neonatal complications are few. Most of these studies were small or did not evaluate a broad scope of possible complications. Therefore, a large population-based cohort study was conducted to study the associations between maternal hyperthyroidism and pregnancy and perinatal complications.

Design: This is a retrospective population-based cohort study utilizing data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample over 11 years from 2004 to 2014.

Patients: 16,984 deliveries to women with hyperthyroidism and 9,079,804 deliveries to mothers who did not suffer of hyperthyroidism.

Methods: A cohort of all deliveries between 2004 and 2014 inclusively was created. Within this group, all deliveries to women with hyperthyroidism were the study group (n = 16,984) and the remaining deliveries were categorized as nonhyperthyroidism births and comprised the reference group (n = 9,079,804). The main outcome measures were pregnancy and perinatal complications.

Results: Maternal hyperthyroidism was associated with several pregnancy and perinatal complications, including increased risks of gestational hypertension (adjusted odds ratio [aOR]: 1.236, 95% confidence interval [CI]: 1.045-1.462, p = .013) and preeclampsia (aOR: 1.190, 95% CI: 1.006-1.408, p = .042). These patients are more likely to experience preterm premature rupture of membranes (aOR: 1.322, 95% CI: 1.007-1.735, p = .044), preterm delivery (aOR: 1.287 95% CI: 1.132-1.465, p < .001), placental previa (aOR: 1.527, 95% CI: 1.082-2.155, p = .016), and suffer from venous thromboembolism (aOR: 2.894, 95% CI: 1.293-6.475, p = .010). As for neonatal outcomes, small for gestational age and stillbirth were more likely to occur in the offspring of women with hyperthyroidism (aOR: 1.688, 95% CI: 1.437-1.984, p < .001 and aOR: 1.647, 95% CI: 1.109-2.447, p = .013, respectively).

Conclusions: Women with hyperthyroidism are more likely to experience pregnancy, delivery, and neonatal complications. We found an association between hyperthyroidism and hypertensive disorders, preterm delivery, and intrauterine fetal death.
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http://dx.doi.org/10.1111/cen.14713DOI Listing
March 2022

Pregnancy, delivery, and neonatal outcomes among women with psoriatic arthritis, a population based study.

J Perinat Med 2022 Jan 21. Epub 2022 Jan 21.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, Montreal, QC, Canada.

Objectives: Many autoimmune diseases negatively affect pregnancies. Studies report conflicting data about the effects of psoriatic arthritis (PsA) in pregnancy. We sought to evaluate the pregnancy, delivery, and neonatal outcomes among women with PsA.

Methods: We conducted a retrospective population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-HIS). Cases of PsA were identified using the ICD code 696.0. Pregnancies complicated with PsA were compared with the other pregnancies. A multivariate logistic regression was used to adjust for confounding variables.

Results: A total of 9,096,369 control births and 419 with PsA occurred during the study period. Women with PsA were more likely to be older, Caucasian, obese, have a higher income, and private insurance (p-value <0.0001 all). Also, they were more likely to start their pregnancy with chronic hypertension, pregestational diabetes, thyroid disorders, inflammatory bowel disease, and depression. Rates of pregnancy induced hypertension (PIH) (aOR 1.58, 95% CI 1.13-2.21) and small for gestational age (SGA) (aOR 2.42, 95% CI 1.49-3.93) were higher in PsA. There were no differences in the rates of most outcomes including: preeclampsia, gestational diabetes, preterm delivery, preterm premature rupture of membranes (PPROM), placenta previa, abruption, modes of delivery, hemorrhage, deep vein thrombosis (DVT), pulmonary embolism (PE), chorioamnionitis, intrauterine fetal death, or congenital anomalies (p>0.05 all).

Conclusions: Women with PsA should be reassured about their pregnancy outcomes as only PIH and SGA were more common. Healthcare providers should take appropriate surveillance and preventive methods to mitigate the effect of these two complications in pregnancies complicated with PsA.
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http://dx.doi.org/10.1515/jpm-2021-0468DOI Listing
January 2022

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

Andrology 2022 May 8;10(4):660-668. Epub 2022 Jan 8.

Division of Reproductive Endocrinology and Infertility, McGill University Health Care Center, Montréal, Québec, Canada.

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.
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http://dx.doi.org/10.1111/andr.13150DOI Listing
May 2022

Histopathological profile of women who had previously failed in-vitro fertilization and the association to the outcome in the subsequent in-vitro fertilization cycle.

Obstet Gynecol Sci 2022 Jan 6;65(1):64-73. Epub 2021 Dec 6.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montreal, Canada.

Objective: To evaluate the endometrial histopathological profile of patients undergoing curettage and the association of the histopathological profile with the pregnancy outcome during the subsequent in-vitro fertilization (IVF) cycle.

Methods: In this retrospective cohort study, a total of 248 women with at least one failed attempt of IVF and who underwent curettage and a subsequent IVF were included. Demographic data, endometrial histopathological records, stimulation information, and pregnancy outcomes were collected and analyzed.

Results: The histopathological analysis of endometrial tissues showed that 130 women (52.4%) had endometrial pathologies. Of these women, 103 (41.5%) had endometrial polyps, 22 (8.9%) had chronic endometritis, and five (2.0%) had both polyps and endometritis. No statistical difference was observed between the normal histopathology group and the abnormal histopathology group in the outcome of the subsequent IVF cycle. Subgroup analyses were performed to further characterize and compare women with normal histopathology and women with endometrial polyps (polyp subgroup) or chronic endometritis (endometritis subgroup). No statistical differences were found among the three groups in the rates of pregnancy (44.1% vs. 49.5% vs. 45.5%, P=0.72), biochemical pregnancy loss (13.5% vs. 15.7% vs. 20.0%, P=0.86), clinical pregnancy loss (25.0% vs. 31.4% vs. 30.0%, P=0.77), and live birth (27.1% vs. 26.2% vs. 22.7%, P=0.91) during the subsequent IVF cycle.

Conclusion: Women with previously failed IVF and abnormal endometrial histopathology treated with curettage had the same outcome in the subsequent IVF cycle as women with normal endometrial histopathology.
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http://dx.doi.org/10.5468/ogs.21229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784933PMC
January 2022

Predıctıve value of pregnancy of follıcular fluıd fetuın-A and -B levels ın infertıle women after intra-cytoplasmic sperm injection.

J Obstet Gynaecol Res 2022 Jan 28;48(1):178-187. Epub 2021 Oct 28.

McGill University Reproductive Center, Montréal, Quebec, Canada.

Aim: We aimed to investigate the value of follicular fluid fetuins-A and -B to predict successful IVF and pregnancy outcomes in infertile women with poor, normal, and high ovarian reserve.

Methods: The follicular fluid of 96 infertile women who underwent intra-cytoplasmic sperm injection (ICSI) procedure was analyzed. Fetuins-A and -B levels were examined and compared in those who could achieve pregnancy and those who could not. Receiver operating characteristic curve analyzes were used to determine cut-off and statistically significant associations for fetuins-A and -B.

Results: Follicular fluid fetuin-A levels were higher in cases with weak ovarian reserve (OR) (p < 0.05) and higher in patients who did not achieve clinical pregnancy (p < 0.05). Conversely, the follicular fluid fetuin-B levels were lower in cases with poor OR (p < 0.05) and were lower in patients who did not achieve a clinical pregnancy (p < 0.05). A follicular fluid fetuin-A concentration ≤ 19.12 ng/mL had a sensitivity and specificity of 94.74% and 93.1%, respectively, at predicting clinical pregnancy. While the follicular fluid fetuin-B concentration >24.7 ng/mL had sensitivity and specificity of 71.1% and 51.7%, respectively, for clinical pregnancy prediction.

Conclusion: Overall, high levels of follicular fluid fetuin-A may be independently associated with unsuccessful IVF irrespective of OR grouping. A low level of follicular fetuin-B was also associated with failed IVF. The sensitivity and specificity were found to be higher for fetuin-A in predicting clinical pregnancy. Therefore, the follicular fluid fetuin-A may be more predictive for successful IVF and clinical pregnancy outcomes than follicular fluid fetuin-B.
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http://dx.doi.org/10.1111/jog.15070DOI Listing
January 2022

The effect of Cushing's syndrome on pregnancy complication rates: analysis of more than 9 million deliveries.

J Matern Fetal Neonatal Med 2021 Aug 29:1-7. Epub 2021 Aug 29.

Division of Reproductive Endocrinology and Infertility, MUHC Reproductive Center, McGill University, Montreal, Quebec, Canada.

Purpose: The purpose of this study to evaluate the risk of Cushing's syndrome (CS) and maternal and fetal complications using the American Nationwide Inpatient Sample database.

Materials And Methods: This is a retrospective study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database from 2004 to 2014. We compared pregnancies with CS versus non-CS regarding pregnancy, delivery, and neonatal outcomes using multivariate logistic regression.

Results: We identified 9,096,788 pregnancies during the study period. Cushing's syndrome complicated 135 pregnancies at a rate of 1-2 cases per 100,000 births. Cushing's syndrome subjects were more likely to be older, obese, have private insurance, chronic hypertension, and pre-gestational diabetes (<.001). The maternal mortality rate was 0.7 and 0.007% in Cushing's syndrome and control groups, respectively, although due to small numbers of cases, this should be interpreted with caution. Preeclampsia was higher in CS compared to controls after controlling for confounding variables, aOR 2.20. Operative vaginal delivery and blood transfusion rates were higher in CS patients than controls after controlling for confounding factors, aOR 6.49 and 3.09, respectively. The rates of preterm delivery (8.9 versus 7.2%) and gestational diabetes (8.1 versus 5.8%) were not statistically different between CS and control groups.

Conclusion: Cushing's syndrome patients begin pregnancies often with maladies making them more at risk for complications including, preeclampsia, blood transfusion, and operative vaginal delivery. These patients might benefit from prevention methods for preeclampsia, and increased surveillance to decrease maternal morbidity and mortality. However, the nature of the database and its limitations, including the lack of information about CS activity and treatments received by patients, warrant careful interpretation of these results.
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http://dx.doi.org/10.1080/14767058.2021.1910658DOI Listing
August 2021

The relation between cigarette smoking with delivery outcomes. An evaluation of a database of more than nine million deliveries.

J Perinat Med 2022 Jan 30;50(1):56-62. Epub 2021 Jul 30.

Division of Reproductive Endocrinology and Infertility, McGill University Health Care Center, Montreal, QC, Canada.

Objectives: Smoking in pregnancy is associated with an increased risk of preterm birth (PTB), intrauterine growth restriction, placental abruption and perinatal death. The association between smoking and other delivery outcomes, such as chorioamnionitis, mode of delivery or postpartum hemorrhage (PPH), however, is insufficient as only few studies addressed these issues. The aim of the study was to evaluate the association between prenatal smoking and delivery outcomes in a large database, while controlling for confounding effects.

Methods: A retrospective population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS). A dataset of all deliveries between 2004 and 2014 (inclusively) was created. Our control group included all pregnant women who did not smoke during pregnancy, which was compared to pregnant women who smoked. A multivariate logistic analysis was conducted, adjusting for any statistically significant confounding effects.

Results: Our study identified 9,096,788 births between 2004 and 2014. Of which, 443,590 (4.8%) had a documented diagnosis of smoking. A significantly higher risk was found for PTB (odds ratio 1.39, CI 1.35-1.43), preterm premature rupture of membranes (odds ratio 1.52, CI 1.43-1.62) and small for gestational age (SGA) neonates (odds ratio 2.27, CI 2.19-2.35). The risks of preeclampsia (odds ratio 0.82, CI 0.78-0.85), chorioamnionitis (odds ratio 0.88, CI 0.83-0.4), PPH (odds ratio 0.94 CI 0.9-0.98) and operative vaginal delivery (odds ratio 0.9, CI 0.87-0.94) were lower among smokers.

Conclusions: This large database confirms the findings of previous smaller studies, according to which smoking decreases the risk of preeclampsia while increasing the risk of PTB and SGA neonates. The current study also revealed a decreased risk for PPH as well as for chorioamnionitis among pregnant smokers.
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http://dx.doi.org/10.1515/jpm-2021-0053DOI Listing
January 2022

Reply by Authors.

J Urol 2021 10 27;206(4):985. Epub 2021 Jul 27.

MUHC Reproductive Centre, McGill University, Montréal, Quebec, Canada.

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http://dx.doi.org/10.1097/JU.0000000000001875.02DOI Listing
October 2021

Is controlled ovarian stimulation and insemination an effective treatment in older women with male partners with decreased total motile sperm counts?

Arch Gynecol Obstet 2022 01 5;305(1):261-266. Epub 2021 Jul 5.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada.

Objective: To assess the effect of the total motile sperm counts (TMSC) on the success of controlled ovarian stimulation (COH) and intra-uterine insemination (IUI) in women 38-42 years of age.

Study Design: A database of all women aged 38-42 years who underwent IUI with stimulation at a University Reproductive Centre between 2009 and 2018 inclusive was developed. Including stimulation with clomiphene citrate, letrozole or gonadotropins and divided into TMSC 5.00-10.0 mil and < 5.00 mil. Statistics were compared with multivariate logistic regression, t tests or Chi-squared tests.

Results: A total of 397 cycles of IUI in 397 patients were included, of which, 190 cycles with TMSC 5.00-10.0 and 207 cycles with TMSC < 5.00. There were no statistical differences in the baseline characteristics between the two groups including: age (P = 0.2), gravidity (P = 0.7), parity (P = 0.6), basal FSH (P = 0.2), basal E2 (P = 0.4), antral follicular count (P = 0.5) and the number of mature follicles stimulated (P = 0.2). As expected, TMSC was 7.6 ± 1.5 mil in the first group and 2.4 ± 1.6 mil in the second group (P < 0.0001). The clinical pregnancy rate per cycle in the 5.01-10.00 TMSC group was 9.5 vs. 3.4% when TMSC < 5.00 (P = 0.01). When evaluating only women 40-42 years of age (99 women in the 5.00-10.00 TMSC group and 95 in the group of TMSC < 5.00); the pregnancy rates were not statistically different between the two groups (7 vs. 7.3%, P = 1), nor was the clinical pregnancy rate (5 vs. 6.3%, P = 0.7).

Conclusions: Women 38-39 years of age have poorer outcomes at COH/IUI when TMSC < 5 million than if it is 5-10 million. Once a woman is 40 years of age, this effect is lost. With TMSC 5-10 million, women 38-39 years of age have respectable outcomes at COH/IUI. Clinical pregnancy rates are very low in women 40 years of age with TMSC ≤ 10 million or 38-39 years old with TMSC < 5 million and other treatments should be offered.
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http://dx.doi.org/10.1007/s00404-021-06091-xDOI Listing
January 2022

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.

Reprod Sci 2022 01 11;29(1):291-300. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, 845 Rue Sherbrooke O, Montréal, H3A 0G4, Canada.

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.
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http://dx.doi.org/10.1007/s43032-021-00649-5DOI Listing
January 2022

Effect of double embryo transfer derived from autologous frozen oocytes on multiple pregnancy rates and presentation of success rates stratified by age at retrieval

J Turk Ger Gynecol Assoc 2021 08 10;22(3):168-173. Epub 2021 Jun 10.

Department of Obstetrics and Gynecology, McGill University Health Center, Montreal, Canada

Objective: To compare outcomes transferring one or two embryos in autologous frozen oocyte cycles.

Material And Methods: A retrospective cohort study conducted at an academic fertility center between January 2012 and December 2018. One-hundred and fourteen patients underwent frozen oocyte transfers; 67 single embryo transfer (SET) and 47 double embryo transfer (DET). No subjects had more than two embryos transferred. Data were analyzed using t-test and chi-squared testing. Multivariate logistic regression was used to control for confounding effects. Power analysis suggested an 82% power with alpha of 5% and effect size of 27%.

Results: Regarding the embryo stage, 72% were cleavage embryos and 28% were blastocyst embryos. Among those who had cleavage stage embryos, 48.8% underwent SET and 51.2% underwent DET. In the blastocyst embryos group these proportions were 84.4% and 15.6%, respectively. There were no difference in pregnancy rate for SET (40.3%) vs DET (36.2%) (p=0.78). Additionally, the live birth rate did not differ between SET and DET (28.4 vs 19.1%, respectively, p=0.26). The multivariate multilevel analysis provided adjusted odds ratios (95% confidence interval) of: 1.85 (0.46-7.44) for pregnancy; 0.497 (0.05-4.86) for clinical pregnancy; and 0.82 (0.11-6.29) for live birth when comparing SET and DET. Multiple pregnancy rates were significantly lower in the SET (0%), compared with DET group (44.4%) (p<0.002).

Conclusion: SET results in excellent live birth outcomes in autologous frozen oocyte cycles. However DET results in significantly increased rates of multiple pregnancies. This suggests that SET is a viable option in autologous frozen oocyte cycles.
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http://dx.doi.org/10.4274/jtgga.galenos.2021.2020.0207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420741PMC
August 2021

Interstitial Cystitis/Bladder Pain Syndrome's Correlations with Pregnancy and Neonatal Outcomes: A Study of a Population Database.

J Urol 2021 10 25;206(4):978-985. Epub 2021 May 25.

MUHC Reproductive Centre, McGill University, Montréal, Quebec, Canada.

Purpose: Our objective was to evaluate the associations with interstitial cystitis during pregnancy using a United States inpatient database.

Materials And Methods: We conducted a retrospective cohort study utilizing the Nationwide Inpatient Sample database from the Healthcare Cost and Utilization Project. ICD-9 code number 595.1 was used to extract cases of chronic interstitial cystitis and these pregnancies were compared to pregnancies without chronic interstitial cystitis, using the Chi-squared test to evaluate nominal variables. A multivariate logistic regression model was subsequently used to adjust for statistically significant confounders (p value <0.05).

Results: There were 9,095,995 deliveries during the study period; 793 pregnant women were found to have chronic interstitial cystitis. When controlling for confounding effects in terms of pregnancy outcomes, the diagnosed group had a greater risk of developing pregnancy-induced hypertension (adjusted OR 1.57, 95% CI 1.21-2.05), preeclampsia (adjusted OR 2.06, 95% CI 1.47-2.87), preterm delivery (adjusted OR 1.63, 95% CI 1.23-2.17), preterm premature rupture of membranes (adjusted OR 2.18, 95% CI 1.25-3.79), chorioamnionitis (adjusted OR 2.05, 95% CI 1.24-3.37), delivery via cesarean section (adjusted OR 1.57, 95% CI 1.32-1.88), maternal infection (adjusted OR 2.19, 95% CI 1.40-3.43), and deep venous thromboembolism (adjusted OR 10.56, 95% CI 3.37-33.09).

Conclusions: Interstitial cystitis diagnosis is associated with an increased risk of preeclampsia, preterm birth, and other adverse pregnancy outcomes in this database study. Prospective studies are required to confirm the findings of the correlation between interstitial cystitis and adverse pregnancy outcomes.
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http://dx.doi.org/10.1097/JU.0000000000001875DOI Listing
October 2021

The impact of timing for estrogen supplementation in polycystic ovary syndrome patients undergoing primed in vitro maturation.

J Obstet Gynaecol Res 2021 Aug 24;47(8):2684-2691. Epub 2021 May 24.

McGill Fertility Center, Department of Obstetrics and Gynecology, McGill University, Montreal, Canada.

Objective: This study aims to determine the effects of early and late onset estrogen supplementation on the immature oocyte retrieval, fertilization and clinical pregnancy rates in follicle stimulating hormone (FSH) and human chorionic hormone (hCG) primed in vitro maturation (IVM) cycles of the patients with polycystic ovary syndrome (PCOS).

Methods: This is a retrospective analysis of 161 patients with PCOS who underwent FSH and hCG primed IVM. Group 1 included 120 patients who received early onset estrogen supplementation while group 2 consisted of 41 patients who had late onset estrogen supplementation in primed IVM cycles. Immature oocyte (germinal vesicle and/or metaphase I) retrieval and fertilization rates were the primary outcomes, whereas clinical pregnancy and live rates were the secondary outcomes.

Results: Group 1 patients had significantly higher body mass index and more previous IVF attempts (p = 0.001 and p = 0.008, respectively). All of the retrieved oocytes from the PCOS patients were either germinal vesicle or metaphase I oocytes and there were no metaphase II oocytes among the retrieved oocytes. Both groups had statistically similar numbers of metaphase I and fertilized oocytes (p > 0.05 for both). However, group 1 patients had significantly lower number of germinal vesicle oocytes but significantly higher number of metaphase II oocytes (p = 0.001 for both). Both groups had statistically similar fertilization (85.0% vs 78.0%), clinical pregnancy (49.2% vs 43.9%) and live birth (37.5% vs 39.0%) rates (p > 0.05 for all).

Conclusion: Early onset estrogen supplementation appears to improve the quality of retrieved immature oocytes and contribute to the maturation of oocytes in stimulated IVM cycles.
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http://dx.doi.org/10.1111/jog.14858DOI Listing
August 2021

Pregnancy, delivery, and neonatal outcomes among women with irritable bowel syndrome (IBS) an evaluation of over 9 million deliveries.

J Matern Fetal Neonatal Med 2021 Apr 6:1-8. Epub 2021 Apr 6.

Division of Reproductive Endocrinology and Infertility, MUHC Reproductive Center, McGill University, Montreal, Canada.

Objective: Evaluate the associations between irritable bowel syndrome (IBS) and pregnancy, delivery, and neonatal outcomes, using a population database cohort.

Methods: We conducted a retrospective analysis utilizing the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database over 11 years from 2004 to 2014. A delivery cohort was created using ICD-9 codes. ICD-9 code 564.1 was used to extract the cases of IBS. Pregnant women with IBS (study group) were compared to pregnant women without IBS (control). A multivariate logistic regression model was used to adjust for statistically significant variables ( value <.05).

Results: There were a total of 9,096,788 deliveries during the study period. Of those, 8962 pregnant women were found to have IBS. The prevalence of IBS increased from 47.96 to 172.68 per 100,000 women during the study period. Compared to the control group, women with IBS were more likely to be Caucasian, older, have higher incomes and private insurance plans ( < .0001, in all cases). In addition, they were more likely to be obese, smokers, hypertensive, IVF pregnancies, have multiple gestations, thyroid disorders, chronic interstitial cystitis, fibromyalgia and have psychiatric disorders ( < .0001 in all cases). Women with IBS were more likely to experience pregnancy-induced hypertension (aOR 1.11, 95% CI 1.02-1.21), preeclampsia (aOR 1.23, 95% CI 1.09-1.38), deep venous thrombosis (aOR 2.26, 95% CI 1.12-4.57), and gestational diabetes (aOR 1.1, 95% CI 1.002-1.22) compared to the non-IBS group. Congenital anomalies were encountered in 1.7% of the IBS group compared to 0.4% in the control group (aOR 2.57, 95% CI 2.13-3.09).

Conclusion: When controlling for confounding effects, IBS is associated with an increased risk for preeclampsia, DVT and increased risk for congenital malformation.
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http://dx.doi.org/10.1080/14767058.2021.1903421DOI Listing
April 2021

Outcomes of donor versus partner sperm in intrauterine insemination in women aged 38 years and older.

Int J Gynaecol Obstet 2022 Mar 19;156(3):516-520. Epub 2021 Apr 19.

Department of Obstetrics and Gynecology, McGill University Health Centre, McGill University, Montreal, QC, Canada.

Objective: To compare pregnancy rates of donor versus partner sperm in intrauterine insemination (IUI) cycles in women aged 38 years and above.

Methods: A retrospective cohort study was performed using data from 944 women aged 38-43 years old who underwent a combined 1596 IUI cycles at an academic fertility clinic in Montreal, Canada between February 2009 to April 2018.

Results: Partner sperm was used in 1421 cycles (89.0%), and donor sperm was inseminated in 175 cycles (11.0%). Mean ages of the women were 39.8 (±1.5) and 40.2 (±1.6) years in the partner and donor insemination groups, respectively (P < 0.001). Positive serum (β human chorionic gonadotropin) pregnancy rate in the partner sperm group was 9.0% (n = 128) whereas that in the donor insemination group was 9.7% (n = 17) (P = 0.759). Clinical pregnancy rates were 5.8% (n = 83) and 8.0% (n = 14) in the respective groups (P = 0.260). There were five multiple gestation (twin) pregnancies in the cohort, three in those undergoing IUI with partner sperm and two in those undergoing IUI with donor sperm.

Conclusion: In women aged 38-43 years undergoing IUI with controlled ovarian stimulation, using donor sperm, compared with partner sperm, did not increase rate of pregnancy.
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http://dx.doi.org/10.1002/ijgo.13694DOI Listing
March 2022

Comparison of in vitro fertilization cycles stimulated with 20 mg letrozole daily versus high-dose gonadotropins in Rotterdam Consensus ultra-poor responders: A proof of concept.

Int J Gynaecol Obstet 2022 Jan 2;156(1):102-106. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada.

Objective: To evaluate if high-dose letrozole can be used successfully to stimulate poor responders for in vitro fertilization (IVF).

Methods: This was a retrospective study conducted at a university hospital reproductive center. The analysis included women who were up to 42 years of age and were Rotterdam Consensus poor responders. A total of 247 patients received gonadotropins (300-450 IU daily) and 62 patients were stimulated with letrozole (20 mg daily) as part of an antagonist IVF protocol.

Results: The use of 20 mg of letrozole decreased the total dose of gonadotropins used (645 ± 175 IU vs. 5360 ± 1028 IU, P = 0.001) and resulted in lower costs of stimulation medications ($ 555.56 ± $ 150 vs. $ 4616 ± $ 885 Canadian Dollars; P = 0.001). Pregnancy per cycle (14.5%) and per transfer (16%) rates were legitimate for this low prognosis group and may have been better than or similar to those with high-dose gonadotropins. The rate of cycle cancellation may have been reduced in the letrozole versus gonadotropin group (11% vs. 38%; P = 0.001).

Conclusion: Letrozole (20 mg daily) may be used to reduce the cost of ovarian stimulation in ultra-poor responders, significantly reducing the cost of the IVF cycle with probably at least similar outcomes to high-dose gonadotropins.
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http://dx.doi.org/10.1002/ijgo.13626DOI Listing
January 2022

Do oral ovulation induction agents offer benefits in women 38 to 43 years of age undergoing insemination cycles?

Eur J Obstet Gynecol Reprod Biol 2021 Mar 12;258:273-277. Epub 2021 Jan 12.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, Montreal, QC, Canada; MUHC Reproductive Center, McGill University, Montreal, QC, Canada. Electronic address:

Objective: To compare the success of ovulation induction using oral agents versus gonadotropins (GTs) in women ≥38 years old.

Study Design: A retrospective cohort study was performed including all first to third stimulated IUI cycles conducted after the age of 38 years in a single academic fertility center between 01/2011 and 03/2018.

Results: A total of 1596 IUI cycles were included. 240 cycles were with clomiphene citrate (CC), 176 letrozole cycles and 1180 gonadotropin (GTs) cycles. The GTs group were older (p < 0.001), had lower antral follicular count (p < 0.001), and thicker endometrium (p < 0.001) compared to the oral agent groups. The letrozole group had a less mature follicles (p = 0.004) at the time of triggering compared to the other groups. No difference in pregnancy or clinical pregnancy rates was observed after controlling for confounders when comparing the 3-groups. 5 multiple pregnancies occurred, all in the GTs group. The groups were subdivided by age; 38-39 years old (N = 750) and 40-43 years old (N = 846). Nevertheless, no statistical difference was observed in pregnancy rates and clinical pregnancy rates between oral agents and GTs when controlling for the confounding effects among women at age 38-39 (p = 0.47, p = 1.0; respectively) and among women 40-43-years-old (p = 0.16, p = 1.0; respectively).

Conclusions: Clearly costs of oral agents are lower and they are more patient friendly than GTs, therefore oral agents should be first line for ovarian stimulation and IUI in women 38-43-years of age.
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http://dx.doi.org/10.1016/j.ejogrb.2021.01.012DOI Listing
March 2021

Blastocyst morphology has no relationship with serum β-hCG levels and live birth rates once pregnant.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 30;258:98-102. Epub 2020 Dec 30.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, Montreal, QC, Canada; MUHC Reproductive Center, McGill University, Montreal, QC, Canada. Electronic address:

Objective: What is the role of blastocyst morphology on day16 β-hCG serum levels and pregnancy outcomes among patients who conceived through IVF cycles with single fresh Gardner's scored blastocyst transfers.

Study Design: A retrospective cohort study conducted at a single academic fertility center between January 2013 and December 2017. A total of 643 pregnancies were included in the study.

Results: The patients were divided into 5 groups according to Gardner's blastocysts grade of the ICM and the TE (grade), and into 4 groups according to blastocyst Gardner's degree of blastocoel expansion (stage). No significant differences were found between the different morphologic groups and day16 β-hCG serum levels, clinical pregnancy rates and live births. A weak significant correlation was observed between Gardner's blastocysts grade and day 16 β-hCG (Correlation Coefficient r= -0.098, p = .014) this correlation remained significant after controlling for confounders. (r= -0.099 p = . 013). A weak significant correlation was observed between Gardner's stage and day 16 β-hCG (Correlation Coefficient r = 0.086, p = 0.029) this correlation lost significance after controlling for confounders. (r = 0.055, p = 0.340). When evaluating predictors of live birth using multivariate logistic regression, blastocyst grade (p = 0.33) and stage (p = 0.65), at transfer, were not associated with live births, when controlling for confounding effects.

Conclusion: Once the patient conceives after IVF with single blastocyst, none of the morphological parameters have a strong impact on the day16 serum level of β-hCG. Among women who conceived, blastocyst grade and stage were not associated with live births.
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http://dx.doi.org/10.1016/j.ejogrb.2020.12.047DOI Listing
March 2021

A comparison of oral versus injectable ovarian stimulation in IUI in women ≥38 years of age with decreased ovarian reserve.

Arch Gynecol Obstet 2021 06 3;303(6):1607-1616. Epub 2021 Jan 3.

Department of Obstetrics and Gynecology, McGill University Health Centre, McGill University, Montreal, QC, Canada.

Purpose: To compare pregnancy rates of oral ovarian hyperstimulation agents (clomiphene citrate (CC) and letrozole) versus injectable agents (gonadotropins) in intrauterine insemination (IUI) in the older reproductive age group with diminished ovarian reserve.

Methods: A retrospective cohort study was performed among 210 women 38-43 years of age undergoing IUI with controlled ovarian hyperstimulation (COH) at a single academic institution between 2009 and 2018.

Results: A total of 335 IUI cycles met inclusion criteria. Gonadotropins were the most frequently used ovarian hyperstimulation agent (n = 264), followed by CC (n = 38) and letrozole (n = 33). Mean age of the cohort was 40.5 (±1.6) years (range 38-43) did not differ significantly among groups (p = 0.41). Mean AFC and number of mature follicles on day of ovulation trigger also did not differ among groups (p = 0.98, p = 0.10). Overall clinical pregnancy rate was 7.5% per cycle, and rates for CC, letrozole, and gonadotropins respectively were 5.3%, 9.1%, 7.5% per cycle (p = 0.347). There was one multiple gestation pregnancy (twins), which was in a patient stimulated with gonadotropins.

Conclusion: This is the first study to compare CC, letrozole, and gonadotropins in older reproductive age women with decreased ovarian reserve. The findings reveal that COH/IUI in older women with decreased ovarian reserve is a viable option (clinical pregnancy rate of 7.5% per cycle), and suggest that oral stimulation agents may be the first-line option, with letrozole having conferred the highest clinical pregnancy rate, 9.1%, which is notable given the typical poor fecundability of this population. However, larger population studies are needed to support this.
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http://dx.doi.org/10.1007/s00404-020-05897-5DOI Listing
June 2021

What Are the Live Birth and Multiple Pregnancy Rates When 1 Versus 2 Low-Quality Blastocysts Are Transferred in a Cryopreserved Cycle? a Retrospective Cohort Study, Stratified for Age, Embryo Quality, and Oocyte Donor Cycles.

Reprod Sci 2021 05 25;28(5):1403-1411. Epub 2020 Nov 25.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility Center, McGill University, 888 Boulevard de Maisonneuve East, suit # 200, Montreal, Quebec, H2l 4S8, Canada.

Outcomes among women who transferred only Gardner's grade BB or lower quality frozen embryos transferred (FET) are not well known. Our objective is to study whether transferring 2 versus 1 frozen low-quality blastocysts will increase the live birth rate (LBR) and the multiple pregnancy rate (MPR). This is a retrospective cohort study including 1104 FET cycles. Only day 5-6 blastocysts of grade BB or lower quality were included. Clinical pregnancy rate (CPR), MPR, and LBR per cycle were compared between single embryo transfer (SET) (n = 969) and double embryo transfer (DET) (n = 135). CPR and MPR were compared between SET and DET in grade BB, BC, CB, and CC individually. Among SET, BB blastocysts had higher CPR 34% (P = 0.0001) and a sub-significant increase in LBR 19% (P = 0.059) in comparison to other grade SET. Among all BB, MPR was significantly higher when transferring two versus one (5.9 vs. 1.9, P = 0.009). If age at egg collection ≥ 40 years (n = 97), no difference was found in CPR (11.1 vs. 11.7, P = 0.9), MPR (0 vs. 0), and LBR (6.3 vs. 0,P = 0.13) when SET or DET was performed. If age was < 40 years (n = 818), the MPR was significantly higher in DET than SET (6.7 vs. 1.63, P = 0.004). In egg donor cycles (n = 189), there was no difference in CPR, MPR, and LBR between SET and DET. Single embryo transfer should be offered even in women ≥ 40 years of age or transferring lower quality embryos since transferring more did not increase outcomes in this group, and SET is likely the safest path.
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http://dx.doi.org/10.1007/s43032-020-00404-2DOI Listing
May 2021

Can in vitro maturation overcome cycles with repeated oocyte maturation arrest? A classification system for maturation arrest and a cohort study.

Int J Gynaecol Obstet 2021 Jun 21;153(3):496-502. Epub 2020 Dec 21.

Department of obstetrics gynecology, McGill University, Montreal, Canada.

Objective: To investigate the role of gonadotropin-stimulated and human chorionic gonadotropin (hCG) -primed in vitro oocyte maturation (IVM) in cases of repeated in vitro fertilization (IVF) failure due to various forms of oocyte maturation arrest (OMA).

Methods: Retrospective cohort study.

Results: In all, 63 women with IVF failure due to OMA were evaluated in this study. According to the Hatirnaz & Dahan classification, 11 (17.5%) women were OMA type 1, 22 (34.9%) were OMA type 2, 0 were OMA type 3, 11 (17.5%) were OMA type 4, and 19 women were OMA type 5 (30.1%). Fewer oocytes were retrieved in the IVM than in the IVF cycles. No embryos were produced from oocytes collected in the IVM cycles of women with OMA types 1, 2, and 4. In the OMA type 5 group, 9 (47.4%) day 2 embryos and 6 (31.6%) day 3 embryos were obtained. The difference between the groups was statistically significant (P = 0.001, P = 0.002, respectively). Single day 3 embryo transfer was performed for the six patients with OMA type 5 but no clinical pregnancies occurred.

Conclusions: Follicle-stimulating hormone-stimulated and hCG-primed IVM does not improve oocyte maturation, developmental potential, or pregnancy rates of women with OMA. Future studies directed to re-establishing normal cytoskeletal architecture and machinery, and resumption of meiosis may be beneficial for obtaining mature oocytes.
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http://dx.doi.org/10.1002/ijgo.13490DOI Listing
June 2021

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

J Assist Reprod Genet 2021 Jan 12;38(1):227-233. Epub 2020 Nov 12.

Department of Obstetrics and Gynecology, McGill University Health Centre, Montreal, QC, Canada.

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.
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http://dx.doi.org/10.1007/s10815-020-01999-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822978PMC
January 2021

COVID-19 pandemic effect on early pregnancy: are miscarriage rates altered, in asymptomatic women?

Arch Gynecol Obstet 2021 03 9;303(3):839-845. Epub 2020 Nov 9.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montréal, QC, H3A 0G4, Canada.

Purpose: To evaluate the effect of the COVID-19 pandemic state on early, first-trimester pregnancies.

Methods: A retrospective cohort study conducted at a university-affiliated fertility center in Montreal, Quebec, since the COVID-19 shut down, March 13 until May 6, 2020. Included: all women who came for a first-trimester viability scan during the study period (Study group) and between March 1, 2019 and May 17, 2019, approximately one year prior (Control). The study population denied symptoms of COVID-19. We reviewed all first trimester scans. Early first-trimester pregnancy outcomes (Viable pregnancy, arrested pregnancy including biochemical pregnancy loss and miscarriage, and ectopic pregnancy) were measured as total number and percentage. A multivariate analysis was performed to control for other potentially significant variables, as was a power analysis supporting sample size.

Results: 113 women came for a first-trimester viability scan in the study period, and 172 in the control period (5-11 weeks gestational age), mean maternal age 36.5 ± 4.5 and 37.2 ± 5.4 years (p = 0.28). Viable clinical pregnancy rate was not different between the two groups (76.1 vs. 80.2% in the pandemic and pre-pandemic groups p = 0.41). No significant difference was seen in the total number of arrested pregnancies (defined as the sum of biochemical, 1st trimester miscarriages, and blighted ova) (22.1 vs. 16.9% p = 0.32), or in each type of miscarriage.

Conclusion: The COVID-19 pandemic environment does not seem to affect early first-trimester miscarriage rates in asymptomatic patients.
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http://dx.doi.org/10.1007/s00404-020-05848-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652042PMC
March 2021

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source.

J Assist Reprod Genet 2020 Dec 26;37(12):3103-3107. Epub 2020 Oct 26.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, MUHC Reproductive Center, McGill University, 888, Blvd. de Maisonneuve East, Suite 200, Montreal, QC, H2L 4S8, Canada.

Purpose: The aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation.

Methods: We performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed.

Results: There were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%).

Conclusions: The use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.
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http://dx.doi.org/10.1007/s10815-020-01976-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714793PMC
December 2020

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

Reprod Biomed Online 2020 Dec 29;41(6):1093-1099. Epub 2020 Aug 29.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, Montréal Quebec H3A 0G4, Canada; MUHC Reproductive Centre, McGill University, Montréal Quebec H2L 4S8, Canada.

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.
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http://dx.doi.org/10.1016/j.rbmo.2020.08.036DOI Listing
December 2020

Effect of newborn gender on placental histopathology and perinatal outcome in singleton live births following IVF.

Reprod Biomed Online 2020 Nov 10;41(5):907-916. Epub 2020 Aug 10.

Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal QC, Canada.

Research Question: Does newborn gender affect placental histopathology pattern and perinatal outcome in singleton live births following IVF treatment?

Design: Retrospective cohort study evaluating data of all live births from one academic tertiary hospital following IVF treatment during 2009-2017. All patients had placentas sent for pathological evaluation irrelevant of maternal and fetal complications status. Exclusion criteria were abnormal uterine cavity findings, previous uterine surgery, in-vitro maturation cycles, gestational carrier cycles, oocyte recipient cycles, preimplantation genetic diagnosis cycles and multiple pregnancies. The primary outcomes included anatomical, inflammation, vascular malperfusion and villous maturation placental features. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate analysis was conducted to adjust the results for factors potentially associated with placental pathology features.

Results: A total of 1057 live births were included in the final analysis and were allocated to the study groups according to fetal gender: males (n = 527) and females (n = 530). After adjustment for potential confounding factors, male gender was significantly associated with villous agglutination (odds ratio [OR] 9.8; 95% confidence interval [CI] 1.4-78.2), avascular villi (OR 4.1; 95% CI 1.3-12.6) and maternal vascular malperfusion (OR 1.8; 95% CI 1.2-2.7). Female gender was significantly associated with bilobed placenta (OR 0.2; 95% CI 0.06-0.8) and subchorionic thrombi (OR 0.5; 95% CI 0.3-0.9). The prevalence of adverse fetal, maternal and delivery outcomes was similar between the groups.

Conclusions: Newborn gender has a significant impact on the placental histopathology pattern, which can contribute to the development of adverse perinatal outcomes.
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http://dx.doi.org/10.1016/j.rbmo.2020.08.002DOI Listing
November 2020

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

Hum Reprod 2020 10;35(10):2213-2225

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montréal, QC, Canada.

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.
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http://dx.doi.org/10.1093/humrep/deaa196DOI Listing
October 2020
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