The aim of our study was to explore the risk factors for very preterm (gestation under 32 weeks) and moderate preterm birth (gestation weeks 32-36 6/7) in singleton pregnancies in a national ...retrospective cohort study. We also wanted to establish whether IVF/ICSI is an independent risk factor for preterm birth after adjusting for already known confounders. We used data for 267 718 singleton births from 2002-2015 from the National Perinatal Information System of Slovenia, containing data on woman, pregnancy, birth, the postpartum period, and the neonate for each mother–infant pair. Mode of conception, maternal age, education, BMI, parity, smoking, history of cervical excision procedure, history of hysteroscopic resection of uterine septum, presence of other congenital uterine malformations, bleeding in pregnancy, preeclampsia or HELLP and maternal heart, and pulmonary or renal illness were included in the analyses. Unadjusted OR for very preterm birth after IVF-ICSI was 2.8 and for moderate preterm birth was 1.7. After adjusting for known confounders, the OR was still significantly elevated (1.6 and 1.3, respectively). Risk factors for very preterm birth with OR higher than 2.4 were history of cervical excision procedure, resection of uterine septum, operation or having other congenital uterine malformations, and bleeding in pregnancy. Risk factors for very preterm birth with OR between 1.4 and 2.1 were age >35 years, being underweight or obese, not having professional education, smoking, first birth, preeclampsia/HELLP, and IVF/ICSI. Risk factors for moderate preterm birth with OR higher than 2.4 were history of cold knife conization and other congenital uterine malformations. We found that even after adjustment, IVF/ICSI represents a single risk factor for early and late preterm birth even after adjustment with other risks such as maternal age, smoking, or a history of invasive procedures for either cervical intraepithelial neoplasia or infertility treatment.
There is a growing number of studies on the association between ambient air pollution and adverse pregnancy outcomes, but their results have been inconsistent. Consequently, a comprehensive review of ...this research area is needed. There was a wide variability in studied pregnancy outcomes, observed gestational windows of exposure, observed ambient air pollutants, applied exposure assessment methods and statistical analysis methods
Gestational duration, preterm birth, (low) birth weight, and small for gestational age/intrauterine growth restriction were most commonly investigated pregnancy outcomes. Gestational windows of exposure typically included were whole pregnancy period, 1st, 2nd, 3rd trimester, first and last gestational months. Preterm birth was the outcome most extensively studied across various gestational windows, especially at the beginning and at the end of pregnancy.
Particulate matter, nitrogen dioxide, ozone, and carbon monoxide were the most commonly used markers of ambient air pollution. Continuous monitoring data were frequently combined with spatially more precisely modelled estimates of exposure.
Exposure to particulate matter and ozone over the entire pregnancy was significantly associated with higher risk for preterm birth: the pooled effect estimates were 1.09 (1.03–1.16) per 10 μg/m3 increase in particulate matter with an aerodynamic diameter of 10 µm or less (PM10),1.24 (1.08–1.41) per 10 μg/m3 increase in particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5), and 1.03 (1.01–1.04) per 10 ppb increase in ozone. For pregnancy outcomes other than PTB, ranges of observed effect estimates were reported due to smaller number of studies included in each gestational window of exposure.
Further research is needed to link the routine pregnancy outcome data with spatially and temporally resolved ambient air pollution data, while adjusting for commonly defined confounders. Methods for assessing exposure to mixtures of pollutants, indoor air pollution exposure, and various other environmental exposures, need to be developed.
Is preterm delivery an infertility treatment-related adverse outcome in infertile women who conceived after reproductive surgery?
Compared with matched fertile women, preterm delivery appears to be a ...modest infertility treatment-related adverse outcome in infertile women who have reproductive surgery then conceived naturally or after IVF/ICSI.
Most observational studies have shown that women who receive any infertility treatment are more likely to deliver preterm than do fertile women. However, studies on the outcome of pregnancies in infertile women who conceive naturally after reproductive surgery are scarce.
This was a single-centre historical two-part study: cohort and matched cohort study. Anonymized data of 761 infertile women who conceived after reproductive surgery and 758 fertile women were obtained by linking three computerized databases from 1 July 2012 to 31 December 2015.
In the cohort study, we evaluated the association between the mode of conception and preterm delivery <37 and <32 gestational weeks in 703 infertile women, with a singleton pregnancy who conceived after reproductive surgery, using logistic regression adjusted for relevant co-variates to calculate the adjusted odds ratio with a 95% CI. In the matched cohort study, we evaluated preterm delivery as infertility treatment-related adverse outcome using the propensity score (PS) method. The matched cohort comprised 758 infertile women and 758 fertile women with a twin or singleton pregnancy. Infertile women conceived after reproductive surgery either naturally or through IVF/ICSI. Infertile and fertile women were matched using PS matching. Infertile and fertile women were matched for pre-defined risk factors for preterm delivery. Three infertile women out of an original 761 were not included in the analysis because they lacked all required matching variables. We performed a 1:1 matching with an optimal matching algorithm with a caliper width of the linear predictor of 0.1 standard deviations. The effect of reproductive surgery on preterm delivery was evaluated in the PS-matched sample using Pearson's χ2 test and presented as the odds ratio (OR) with 95% CI. All women delivered at the Department of Perinatology, University Medical Centre Ljubljana, Slovenia.
Among 761 infertile women who conceived after reproductive surgery, 428 (56.2%) women conceived naturally and 333 (43.8%) conceived after IVF/ICSI. The incidence of twin pregnancies was significantly lower after natural conception (2.6% vs 14.1%). Among the 703 infertile women with a singleton pregnancy, 417 (59.3%) conceived naturally and 286 (40.7%) conceived after IVF/ICSI. Adjusted for maternal age and parity in infertile women with singleton pregnancies, IVF/ICSI showed a moderate association with preterm delivery <32 weeks. Compared with natural conception after reproductive surgery, the odds for preterm delivery after IVF/ICSI was 1.07 (95% CI 0.63-1.81) <37 weeks and 2.25 (95% CI 0.80-6.34) <32 weeks. Preterm delivery appears to be a modest infertility treatment-related adverse outcome. Compared with fertile women in the PS-matched sample, infertile women who conceived after reproductive surgery either naturally or after IVF/ICSI the odds of preterm delivery <37 weeks were 1.31 (95% CI 0.97-1.78) and odds of preterm delivery <32 weeks were 1.57 (95% CI 0.78-3.18). However, none of the estimations were statistically significant.
The main limitations of the study were the retrospective design, the heterogeneity of the types of reproductive surgery performed and underlying reproductive pathologies. The low number of preterm deliveries in the present study might influence the precision of estimations.
The present study aims to alter the prevailing opinion that reproductive surgery should only be considered preceding IVF to increase implantation and pregnancy rates after IVF. It implies that in selected infertile women who have had reproductive surgery, a high rate of natural conception, a low rate of multiple pregnancies, and a modest infertility treatment-related effect on preterm delivery should be the reasons to encourage natural conception after reproductive surgery. Furthermore, by allowing for natural conception, we can avoid a high-cost invasive medical procedure.
The study received no funding. We have no competing interest to declare.
N/A.
Background: We reviewed the literature comparing the pathological characteristics of singleton births conceived after assisted reproductive technology (ART) with those after spontaneous conception. ...Methods: We reviewed PubMed, EMBASE, Ovid MEDLINE, Google Scopus, Scholar, Cochrane Central Register of Controlled Trials and the Web of Science for the previous 10 years, up to November 2022. Results: Four eligible studies included 3445 placentas, 806 after ART (IVF/ICSI). Placentas after ART differed in frequency of retroplacental and marginal hematomas (p = 0.04), increased thickness (p = 0.02), higher overall occurrences of vascular and anatomical pathology (p < 0.001) and more frequent marginal (p = 0.001) and membranous (p = 0.02) umbilical cord insertion than placentas from non-ART pregnancies. Conclusion: Further research is needed to determine the extent to which these placental changes in ART pregnancies alter its function and pregnancy outcome.
Background and Objectives: Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, ...is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. Materials and Methods: This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. Results: In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; p = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 95% CI 0.87–1.29). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 95% CI 0.26–0.95; p = 0.036) or superficial implants (aOR 0.88 95% CI 0.58–0.95; p = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. Conclusions: When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study’s limitations.
Hysteroscopic septum dissection (HSD) is thought to improve fertility and pregnancy outcomes. However, the available literature suggests that uterine surgery can cause placental abnormalities in ...subsequent pregnancies.
A case-control study was performed at the University Medical Center of Ljubljana, Department of Human Reproduction, from 1 January 2016 to 31 December 2018. The primary outcome was the association between HSD and the occurrence of placental abnormalities. We included women who underwent HSD due to infertility. Age-matched women who underwent hysteroscopic surgery for other issues were considered as controls. In addition, we divided the groups according to conception method. Only singleton pregnancies and first delivery were considered.
A total of 1286 women (746 who underwent HSD and 540 controls) were included in the analysis. HSD had no influence on placental abnormalities since the ratio was comparable regardless of the method of conception (113/746 vs. 69/540;
= 0.515). Infertile women who conceived naturally after HSD had a normal placentation rate comparable to women who did not undergo HSD (380/427 vs. 280/312;
= 0.2104). The rate of placental abnormalities in women who achieved pregnancy with IVF/ICSI procedures following HSD was comparable to that of women who did not undergo HSD (52/319 vs. 33/228;
= 0.5478). Placenta previa occurred significantly more often in infertile women without HSD after IVF/ICSI compared to natural conception (2/312 vs. 7/228;
= 0.0401).
HSD was not associated with higher rate of placental abnormalities in the first singleton pregnancy compared with other hysteroscopic procedures. A higher rate of placenta previa in pregnancies following IVF/ICSI procedures, which was shown by our research, is corroborated by previous research findings.
While triggering oocyte maturation with GnRH agonist (GnRHa) seems to be safe and effective in terms of the risk of developing OHSS and the number of metaphase II oocytes, it nevertheless results in ...luteal phase deficiency. To date, strategies have been developed in order to rescue defective luteal phase of GnRHa triggered cycles. Our study aimed to assess the reproductive outcome of GnRHa triggered cycles combined with modified luteal support (1500 IU hCG at the day of oocyte retrieval) in women with high ovarian response and to compare the outcome with hCG triggered cycles in GnRH antagonist IVF-ICSI procedures. A retrospective cohort database review of the results of GnRH antagonist IVF-ICSI cycles was conducted at a tertiary-care IVF center in Ljubljana, Slovenia. A total of 6126 cycles, performed from January 1, 2014, to December 31, 2020, were included in the final analysis. Final oocyte maturation was performed with either 5000, 6500, or 10,000 IU hCG (women with normal ovarian response) or 0.6 mg GnRHa (buserelin), supplemented with 1500 IU hCG on the day of oocyte retrieval (in women with high ovarian response). In cases of excessive ovarian response and/or high risk of OHSS luteal support was not introduced and all good quality blastocysts were frozen. According to significant differences in patients' age and the number of oocytes in the two groups, matching by age and number of oocytes was performed. No significant differences were observed regarding pregnancy rate per embryo transfer, rate of early pregnancy loss, and livebirth rate per pregnancy between the GnRHa and hCG trigger groups, respectively. A significant difference in the number of developed embryos and blastocysts, as well as the number of frozen blastocysts, was seen in favor of the GnRHa trigger. However, the birth weight in the GnRHa trigger group was significantly lower.
The results of our study support the use of GnRHa for final oocyte maturation in GnRH antagonist IVF cycles in women with high ovarian response. Luteal phase rescue was performed by co-administration of 1500 IU hCG on the day of oocyte retrieval and estradiol and progesterone supplementation. In our experience, such an approach results in a comparable reproductive outcome with hCG trigger group.