We postulated that impaired endometrial differentiation in women with pelvic endometriosis predisposes for pre-eclampsia.
Methods
A retrospective case-control study set at the University of Ghent IVF centre. The incidence of pre-eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or laparoscopic diagnosis of endometriosis-associated infertility (case group; n = 245 pregnancies) was compared with the incidence of these obstetric complications in pregnancies following treatment for male-factor infertility (control group; n = 274 pregnancies). Pregnancy data were obtained by searching electronic databases and postal questionnaires. The case and control groups were matched for age, parity and multiple pregnancies.
Results
The incidence of pre-eclampsia was significantly lower in the case group (0.8%) when compared with control group (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7-33.3). Analysis of obstetric outcome in the subgroup of patients with laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%) versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2-37). PIH occurred in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR = 2.6, 95% CI: 1.2-6.0). The odds of developing pre-eclampsia were 5.67 times higher in the control group than in pregnancies following endometriosis-associated infertility. In multiple pregnancies, the odds of developing pre-eclampsia increased 1.93 times per additional child, with or without endometriosis.
Conclusions
We found no evidence that endometriosis predisposes for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is significantly reduced in women with endometriosis-associated infertility.
PMID 17452394 17452394 DOI 10.1093/humrep/dem072 10.1093/humrep/dem072
Cite this article
Brosens, I. A., De Sutter, P., Hamerlynck, T., Imeraj, L., Yao, Z., Cloke, B., Brosens, J. J., & Dhont, M. (2007). Endometriosis is associated with a decreased risk of pre-eclampsia. Human reproduction (Oxford, England), 22(6), 1725-1729. https://doi.org/10.1093/humrep/dem072
Brosens IA, De Sutter P, Hamerlynck T, Imeraj L, Yao Z, Cloke B, et al. Endometriosis is associated with a decreased risk of pre-eclampsia. Hum Reprod. 2007;22(6):1725-1729. doi:10.1093/humrep/dem072
Brosens, I. A., et al. "Endometriosis is associated with a decreased risk of pre-eclampsia." Human reproduction (Oxford, England), vol. 22, no. 6, 2007, pp. 1725-1729.
To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.
Reports suggest that there is an increased incidence of preeclampsia after a previously normal pregnancy if there is a change in paternity. We hypothesize that there is a higher incidence of preeclampsia (proteinuric hypertension) in women conceiving by intrauterine insemination with donor sperm versus intrauterine insemination with partner sperm. This was a retrospective cohort study. In women with primary infertility all pregnancies achieved by either partner or donor intrauterine insemination carried to birth of a fetus (> 20 weeks) were identified. The medical records were examined for the maternal and pregnancy outcome data. The relative risk and 95% confidence interval were calculated for the risk of preeclampsia. The baseline data were compared with t tests, chi 2 analysis and Fisher's exact test where appropriate. Forty-four patients in the partner intrauterine insemination group and 37 in the donor insemination group were identified as having primary infertility. Three cases of mild preeclampsia were found in the partner insemination program and nine cases of preeclampsia (five severe, four mild) in the donor insemination program (relative risk 1.85, 95% confidence interval 1.20 to 2.85). There is a higher incidence of preeclampsia in women conceiving by intrauterine insemination with washed donor sperm compared with intrauterine insemination with washed partner sperm. This supports, indirectly, an immunologic basis for preeclampsia. The antigenic factor would appear to be located on the sperm as opposed to the seminal fluid itself.
InfertilityFrozen Embryo TransferPreeclampsia Risk FactorsPAPP-A and IGF-1
Mørch NF et al., 2026·Human reproduction (Oxford, England)
Are maternal concentrations of pregnancy-associated plasma protein-A (PAPP-A) and insulin-like growth factor-1 (IGF-1) influenced by the frozen embryo transfer (FET) protocol in early pregnancy? Maternal concentrations of PAPP-A and IGF-1 were significantly lower in programmed cycle (PC) FET compared to modified natural cycle (mNC) FET among ovulatory women and compared to gonadotrophin-stimulated cycle (gSC) FET in anovulatory women. PC-FET has been associated with increased risks of preeclampsia and other placenta-related complications, pointing to altered placental development. PAPP-A and IGF-1 are biochemical markers of early placental function, and reduced levels have been linked to preeclampsia and other adverse outcomes. These markers may therefore provide insight into the pathways underlying the distinct risk profile of PC-FET. STUDY DESIGN, SIZE, This is a secondary analysis from a randomized controlled trial investigating estradiol and progesterone concentrations in FET treatments. The trial was conducted at Copenhagen University Hospital-Herlev, Denmark, from April 2021 to December 2024. Biochemical analyses for PAPP-A and IGF-1 were performed on stored biobank samples from the trial. The main analyses included women with ongoing pregnancies (n = 116), while additional analyses of IGF-1 were conducted in all ovulatory women with available biobank samples (n = 193). PARTICIPANTS/MATERIALS, SETTING, Eligible participants were women aged 18-40 years with BMI ≤35 kg/m2 undergoing frozen-thawed autologous blastocyst transfer. Ovulatory women were randomized to mNC or PC, and anovulatory women to gSC or PC. Samples were collected at the following 7 timepoints on the 2nd or 3rd day of menstrual bleeding, on the day of trigger/endometrial thickness ≥7 mm, on the day of embryo transfer and by gestational ages (GA) 4 + 2, 6 + 0, 8 + 0, and 9 + 6. Data on placental weight were collected at delivery. MAIN The present analyses included women with ongoing pregnancies 43 in the ovulatory mNC group, 42 in the ovulatory PC group, 16 in the anovulatory gSC group, and 15 in the anovulatory PC group. PC had substantially lower IGF-1 concentrations from treatment initiation through GA 8 + 0 compared to both mNC and gSC. Ovulatory women treated with PC showed significantly lower PAPP-A concentrations during endometrial preparation (7.4 vs 8.7 mU/l; adjusted P = 0.02), at embryo transfer (6.7 vs 8.8 mU/l; adjusted P < 0.001), and GA 4 + 2 (7.2 vs 8.5 mU/l; adjusted P = 0.03) than women treated with mNC. Among anovulatory women, PAPP-A concentrations were also reduced during endometrial preparation (5.8 vs 9.1 mU/l; adjusted P = 0.008) in PC compared to gSC. LIMITATIONS, As this was a secondary analysis, no formal power calculation was made, and statistical power may therefore be limited. We provide evidence that PC-FET was followed by lower IGF-1 concentrations in early pregnancy and by time-dependent reductions in PAPP-A compared to mNC-FET and gSC-FET. These findings suggest alterations in early placental biology that may contribute to the adverse obstetric risk profile associated with PC-FET. Future studies should clarify whether these changes are related to the use of oral estradiol and whether alternative administration routes could modify this risk. STUDY FUNDING/COMPETING INTEREST(S): The trial was funded by Gedeon Richter Nordics AB, including analysis of biobank samples (grant numbers DK-2019-04, DK-2022-03, DK-2023-08, DK-2023-06, DK-2024-08). The trial also received one grant from the Gangsted-Rasmussen Foundation (grant number A39784) and a grant was obtained from the local research board at Copenhagen University Hospital-Herlev. The study was designed and planned independently, with no involvement from the funders in data analysis or interpretation of the results. N.F.M. has received funding for congress attendance from Gedeon Richter Nordics AB and Merck A/S, unrelated to the present work. B.N. has received grants to the institution from Merck A/S, Gedeon Richter Nordics AB, and Ferring Pharmaceuticals A/S, along with personal fees from Ferring Pharmaceuticals A/S, travel support from Gedeon Richter Nordics AB, and has participated in a data safety monitoring or advisory board for Ferring Pharmaceuticals A/S, outside of this research. M.K. has received funding from Rigshospitalets Research Board outside of this research. L.R. has received a research grant from the Novo Nordisk Foundation outside of this research. P.F.S. has received grants from Merck A/S, Gedeon Richter Nordics AB, and Ferring Pharmaceuticals A/S, travel support from Ferring Pharmaceuticals A/S, and personal fees from Novo Nordisk for webinars, outside of this study. 2020-001218-39 in EudraCT.
Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height? We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche. Dietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche. STUDY DESIGN, SIZE, The Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively. PARTICIPANTS/MATERIALS, SETTING, We included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height. MAIN Six thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004). LIMITATIONS, Self-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome. Our findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose. N/A.