Genetics and Immunology · Reproductive Genetics
Yong PJ, Langlois S, von Dadelszen P, Robinson W
Prenatally diagnosed trisomy 16 mosaicism is associated with the increased risk of poor pregnancy outcome including intrauterine growth restriction, intrauterine death and fetal malformation. While maternal preeclampsia has also been reported in some cases, this has not been systematically evaluated.
To better define the risk of preeclampsia and the clinical course of preeclampsia in these pregnancies and to identify associated clinical variables, we reviewed 25 cases of prenatally diagnosed trisomy 16 mosaicism for which molecular studies were undertaken and sufficient obstetrical data were present to include/exclude the diagnosis of preeclampsia.
Six of 25 (24%) mosaic trisomy 16 cases exhibited preeclampsia as compared to 3 of 44 (7%) matched controls. There were no differences between those mosaic trisomy 16 cases presenting with preeclampsia and those that did not, in terms of the presence/absence of UPD, IUGR, malformation, or trisomy on amniocentesis. Four of the 6 (67%) preeclampsia-associated fetuses were male, compared with only 4 of 19 (21%) (p = 0.06) nonpreeclampsia case fetuses, and three of these also had hypospadias. The levels of trisomy tended to be high in placentas associated with preeclampsia; however very high levels of placental trisomy were also often seen in the absence of preeclampsia.
As it is impossible to predict which subset of cases is at highest risk, all women receiving a prenatal diagnosis of trisomy 16 mosaicism should be closely monitored for signs of preeclampsia.
Rojas HE et al., 2026 · Journal of women's health (2002)
To characterize differences between individuals with and without mid-cycle pain in a registry cohort with endometriosis. Prospective analysis of data from the Endometriosis Pelvic Pain Interdisciplinary Cohort Data Registry (Clinicaltrials.gov #NCT02911090) at a tertiary referral center in Western Canada. Three hundred forty-five individuals aged 18-49 years who: (1) had at least one episode of menstrual bleeding in the last 3 months, (2) attended a baseline initial visit, and (3) subsequently had surgery with histological confirmation of endometriosis between January 2018 and December 2023. Exclusion criteria included (1) previous hysterectomy; (2) hormonal suppressive therapy use in the last 3 months; and (3) missing data on mid-cycle pain, history of hormonal therapy use, or menstrual cycle regularity. N/A. Mid-cycle pain in the last month versus No mid-cycle pain in the last month. Of the 345 participants, 67% (n = 232) reported mid-cycle pain in the last month. Mid-cycle pain in the last month was significantly associated with higher mean Central Sensitization Inventory score (48 ± 17 versus 36 ± 16, p < 0.001) and more months of prior hormonal suppressive therapy use (58 [14-120] versus 26 [0-109], p = 0.012). Abnormal anatomy at the time of surgery (e.g., endometrioma, ovarian adhesions) was not associated with mid-cycle pain in the last month. In this endometriosis cohort at a tertiary referral center, most participants reported mid-cycle pain in the last month, which was associated with central sensitization but was not clearly related to endometriosis anatomical distortion.
Bouchard TP et al., 2026 · Reproductive biomedicine online · Free to read
Do quantitative urinary hormone measurements on the Mira monitor predict and confirm ovulation accurately compared with ultrasound in women with regular menstrual cycles? Do Mira urine hormones correlate with serum hormones? This was a prospective, single-centre, blinded diagnostic accuracy study with 52 women aged 19-44 years with regular cycles (24-38 days) who tracked 153 cycles over 18 months. Daily first-morning urine was tested with the Mira monitor for follicle stimulating hormone (FSH), oestrone-3-glucuronide (E13G), luteinizing hormone (LH) and pregnanediol glucuronide (PDG). Serial transvaginal ultrasounds (890 scans) confirmed the day of ovulation. Serum hormones were measured twice per cycle. The 121 ovulatory cycles from 49 participants with sufficient index test and reference standard data were included in the final analysis. The Mira LH peak day strongly predicted ultrasound-confirmed ovulation (R² = 0.96, P < 0.001; intraclass correlation coefficient = 0.971), with 96% of ovulations occurring within ±1 day. The Mira PDG increase was also strongly associated with ultrasound-confirmed day of ovulation (R² = 0.87, P < 0.001). First-morning urine hormones were significantly associated with serum hormones when collected within 90 min (LH: R² = 0.92; E13G: R² = 0.73; R² = 0.61; R² = 0.75). Anovulatory cycles were identified in 11% of regularly cycling participants. Quantitative urinary hormone monitoring with the Mira monitor provides accurate prediction and confirmation of ovulation, with strong urine-serum associations supporting reduced reliance on serial serum draws in select patients. These findings support clinical adoption of quantitative urinary fertility monitoring.
Balachandran S et al., 2026 · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes. This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth. 544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003). Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Bouchard TP et al., 2026 · Reproductive biomedicine online · Free to read
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Yong PJ et al., 2009 · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
Mosaicism with trisomy confined to the placenta is present in ~1% of ongoing pregnancies at the time of chorionic villus sampling. Some studies have found reduced fetal growth in confined placental trisomy. The objective of this study was to assess placental weight and feto-placental weight ratio in pregnancies with trisomy confined to the placenta, and to correlate them with the level of trisomy in the three major placental lineages. We conducted a retrospective study of 69 pregnancies with prenatally diagnosed mosaic trisomy in which the trisomic cells were confined to the placenta. Placental weight and feto-placental weight ratio were compared to those of matched controls, and placental weight was also analyzed for associations with the type and level of trisomy. Placental pathology was also reviewed. The pregnancies with mosaic trisomy were found to have lower placental weights than matched controls, but normal feto-placental weight ratios. Placental weight was not associated with the type or level of trisomic cells in the three placental lineages at term (chorionic plate, chorionic villus mesenchyme, and trophoblast). There were no pathognomonic findings on routine placental pathology of the trisomic placentas. Although placental weight was reduced (with normal feto-placental weight ratio) in pregnancies with trisomy confined to the placenta, the level of placental trisomy was not correlated with placental weight. Thus, trisomy may alter placental function rather than have a direct hypoplastic effect on placental growth. More in-depth studies beyond routine pathology are required to identify how trisomy affects placental function.
Yong PJ et al., 2002 · American journal of medical genetics
Although a number of infants with maternal uniparental disomy of chromosome 16 (upd(16)mat) have been reported, the evidence for imprinting on chromosome 16 is not yet conclusive. To test the hypothesis that upd(16)mat has a distinct phenotype, which would support the existence of imprinted gene(s) on chromosome 16, statistical analysis was performed on a large series (n = 83) of mosaic trisomy 16 cases with molecular determination of uniparental disomy status. The incidence of upd(16)mat was 40%, which is consistent with the expected one third from random chromosome loss during trisomy rescue (P = 0.262). In pairwise comparisons, upd(16)mat was found to be associated with fetal growth restriction (P = 0.029) and with increased risk of major malformation (RR = 1.43; P = 0.053). Regression modeling showed that the effect of upd(16)mat on fetal/neonatal weight and malformation is independent of the degree of trisomy detected in the fetus. Regression modeling to control for the degree of trisomy detected in the placenta was not possible due to limited sample size. We conclude that upd(16)mat is associated with more severe growth restriction, and possibly, with higher risk of malformation. Our hypothesis is that imprinted gene(s) exist on chromosome 16 and that abnormal expression of these gene(s) in upd(16)mat cells during development results in decreased cell proliferation. Although we do not advocate prenatal testing for upd(16), studies on the long-term outcome of upd(16)mat neonates is necessary for counseling purposes.
Yong PJ et al., 2003 · Journal of medical genetics · Free full text on PubMed Central
Analysis of data from cases of trisomy mosaicism can provide insight for genetic counselling after prenatal diagnosis and for the elucidation of the pathogenesis of trisomy during pregnancy. Statistical analysis was carried out on data from 162 cases of pregnancies with prenatal diagnosis of trisomy 16 mosaicism. The majority of cases resulted in live birth (66%) with an average gestational age of 35.7 weeks and average birth weight of -1.93 standard deviations from the population mean. Among the live births 45% had at least one malformation, the most common being VSD, ASD, and hypospadias. The level of trisomy on direct CVS (cytotrophoblast) was associated with more severe intrauterine growth restriction (IUGR) and higher risk of malformation, while the level of trisomy on cultured CVS (chorionic villous stroma) was associated only with more severe IUGR. Similarly, the presence of trisomy on amniocentesis (amniotic fluid) was associated with both IUGR and malformation, while the presence of trisomy in the amniotic mesenchyme was associated only with IUGR. Surprisingly, the degree of trisomy in placental tissues appeared to be independent of the degree of trisomy in amniotic fluid and amniotic mesenchyme. The sex of the fetus was not associated with any outcome variables, although there was an excess of females (sex ratio = 0.45) that may be explained by selection against male mosaic trisomy 16 embryos before the time of CVS (approximately 9-12 weeks). The levels of trisomy in different fetal-placental tissues are significant predictors of some measures of outcome in mosaic trisomy 16 pregnancies.
Langlois S et al., 2006 · Prenatal diagnosis
To determine the long-term outcome of pregnancies prenatally diagnosed with trisomy 16 and identify variables associated with the outcome. We reviewed all published and our unpublished data from trisomy 16 pregnancies for which outcomes were available for children of greater than 1 year of age. Nineteen cases were diagnosed with trisomy 16 on chorionic villus sampling (CVS) and 17 cases at amniocentesis. Age at last follow-up ranges from 1 to 13 years. Among the CVS group, four out of five patients, with a birth weight and/or length below -2 SD and postnatal growth information, showed catch-up growth (80%). Among the amniotic fluid (AF) group, the birth weight was available in 13 cases. Eleven of the 13 cases had a birth weight less than -2 SD. In eight cases, the length was also below -2 SD (length data unavailable in one case). Nine out of ten cases (90%) and seven out of eight (87.5%) showed catch-up growth for weight and length, respectively. In terms of development, no cases of CVS mosaicism had global developmental delay. One child had a history of delay in speech development. Among the AF-detected cases, 4/17 cases had global developmental delay. All four children with global developmental delay had more than one major malformation compared to 6 out of 32 children in the group with normal development (p = 0.004). The finding of uniparental disomy (UPD) was not associated with developmental delay. The majority of prenatally diagnosed trisomy 16 mosaic cases have a good postnatal outcome. However, the finding of mosaicism on AF and the presence of major congenital anomalies are associated with an increased risk of developmental delay.
