Michela Villani

Risk of obstetric and thromboembolic complications in family members of women with previous adverse obstetric outcomes carrying common inherited thombophilias.

Summary.  Background: Factor (F)V Leiden and the prothrombin 20210A mutation (PTm) are associated with the occurrence of obstetric complications, including pregnancy‐related venous thromboembolism (VTE). It is not known whether family members of women with FV Leiden or PTm and previous obstetric complications have a higher risk of VTE or adverse obstetric outcomes. Methods: A retrospective family study including 563 relatives of 177 women with previous adverse outcomes carrying FV Leiden or PTm, referred between April 1993 and June 2010. A history of obstetric complications and VTE was obtained. Prevalence of VTE and obstetric complications in relatives with and without inherited thrombophilias was compared. Adjusted odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models that controlled for predictors (age, FV Leiden and PTm). Results: Relatives carrying FV Leiden had a significant and independent risk for obstetric complications (OR: 1.98, 95% CI 1.03–3.83); this risk was not observed in the presence of PTm (OR: 1.03, 95% CI 0.46–2.32). The presence of FV Leiden or PTm in heterozygosis was significantly and independently associated with the occurrence of VTE (OR: 5.2, 95% CI: 1.70–15.91). Severe thrombophilias were strong risk factors for VTE (OR: 23.2, 95% CI: 6.0–89.85). Male gender was a significant and independent risk factor for VTE (OR: 3.49, 95% CI: 1.51–8.05). The risk did not change when relatives of women with a previous pregnancy‐related VTE were excluded (OR: 3.49, 95% CI: 1.51–8.05). Conclusions: Knowledge of thrombophilia status may help to better define the obstetric and thromboembolic risks in asymptomatic family members of women who suffered from obstetric complications.

Aspirin and heparin in pregnancy.

Introduction: A pro-coagulant state during pregnancy can be involved in the occurrence of gestational vascular complications (GVCs) and venous thromboembolism (VTE). Areas covered: Antithrombotic drugs are used to prevent GVCs and VTE. Aspirin is not efficacious to prevent recurrences in women with previous early loss, while it can prevent pre-eclampsia in some groups of women. Heparins are not effective in the prevention of early recurrent loss and there is uncertainty about their efficacy in women carrying inherited thrombophilias. They could be efficacious in the prevention of GVCs in carriers of inherited thrombophilias, as GVCs have heterogeneous causes, and future studies have to focus on more homogeneous groups of patients. Not enough data are available regarding prophylaxis with heparins to prevent pregnancy-related VTE, but an accurate risk stratification of women during pregnancy and puerperium is crucial for administering prophylaxis in moderate-/high-risk women. Aspirin does not improve live births after assisted reproductive technologies, while heparins increase the number of clinical pregnancies and live births. Expert opinion: Aspirin is efficacious in the prevention of GVCs in women at risk for pre-eclampsia and in those with antiphospholipid antibodies syndrome. Heparins could give benefit to women at risk for GVCs and/or pregnancy-related VTE.

Pregnancy-related venous thrombosis: comparison between spontaneous and ART conception in an Italian cohort.

Objective To evaluate in an Italian cohort the incidence of venous thromboembolic events (VTE) in pregnancies after assisted reproductive technologies (ART). Setting Thrombosis and Haemostasis Unit at I.R.C.C.S. ‘Casa Sollievo della Sofferenza’, S. Giovanni Rotondo. Participants A prospective cohort of 998 women advised to undergo ART was referred by local fertility clinics from April 2002 to July 2011. Follow-up information was obtained during the check-up and/or by phone interviews. In a cohort of women who consecutively gave birth (n=3339) after spontaneous conception in our Institution, information on the diagnoses of pregnancy-related venous thromboses was obtained by linkage to a patient administrative register. Primary and secondary outcome measures We calculated the incidence of VTE and superficial venous thrombosis in successful ART cycles and compared it with that of the general population conceiving spontaneously. Results Overall, 684 ART cycles were carried out by 234 women, who achieved a clinical pregnancy; in case of more than one successful cycle, only the first pregnancy was considered. Three vein thromboses (two VTE and one superficial vein thrombosis) were recorded. An antithrombotic prophylaxis with LMWH alone or combined with low-dose aspirin was prescribed in 23/234 (9.8%) women. In the reference cohort of 3339 women, a total of 11 vein thromboses were observed: six VTE and five SVT. The two-tailed Fisher exact test showed a trend towards statistical significance (p: 0.06, OR: 3.9, 95% CI 0.87 to 15.3). After the exclusion of superficial thromboses in both the groups, we found that the incidence of VTE in our population of women who had undergone ART was 2/234 pregnancies (8.5 ‰), whereas that in our reference population was 6/3339 (1.8 ‰) (p: 0.09). Conclusions Our data show a slightly higher incidence of vein thromboses in pregnancies after ART than in those after natural conception.

Assisted reproductive technologies and thrombosis

In this article, we address issues about thrombotic risk and use of antithrombotic prophylaxis during assisted reproductive technologies (ART) and during pregnancies after ART. Many aspects of these complications remain not completely understood and data about incidence, pathogenesis, duration and magnitude of the risk, role of thrombophilias and thromboprophylaxis in determining first events and recurrences are lacking. The role of known or possible risk factors and the efficacy of antithrombotic prophylaxis will be discussed.

Low-molecular -weight heparin in pregnancies after ART -A retrospective study-

INTRODUCTION The utility of an antithrombotic prophylaxis in Assisted Reproductive Technologies (ART) is highly debated. It has been hypothesised that specific effects of heparin on the coagulation system during implantation can improve the number of clinical pregnancies and live births. MATERIALS AND METHODS We studied a cohort of 327 women undergone at least 1 ART cycle before thrombophilia testing. Overall, a number of 751cycles was analysed. Low-Molecular-Weight Heparin (LMWH) and/or low-dose aspirin (ASA) were prescribed in 132 (17.6%) cycles. Furthermore, all the women underwent thrombophilia screening. RESULTS The univariate analysis showed that LMWH with/without ASA was significantly associated with both the outcomes clinical pregnancy and live birth, while the use of ASA was not associated with live birth. The logistic regression showed that the use of LMWH was significantly associated with both the outcomes, clinical pregnancy (OR: 6.0, 95%CI: 2.8-15.6) and live birth (OR: 10.7, 95%CI: 3.2-36.1). The type of ART procedure significantly influenced the likelihood of achieving clinical pregnancy. CONCLUSIONS Present findings suggest that LMWH alone or combined with ASA could have a role in fostering the implantation of embryos and improving the number of live births after ART.

Clinical Utility of Antithrombotic Prophylaxis in ART Procedures: An Italian Experience

Background The usefulness of antithrombotic prophylaxis in management of Assisted Reproductive Technologies (ART) is questionable. Objectives We prospectively examined the contribution of an antithrombotic prophylaxis in influencing clinical pregnancy and live-birth in an unselected cohort of women approaching ART. Patients/Methods 1107 women with fertility problems and a valid indication for ART were recruited. Baseline and follow-up information of obstetric outcomes and antithrombotic treatment were collected. Results and Conclusions Median follow-up time was 34.5 months (range: 2–143). During the follow-up period, 595 (53.8%) women underwent ART (total 1234 cycles); 202 (33.9%) women achieved a pregnancy for a total of 255 clinical pregnancies. The concomitant use of LMWH and aspirin was significantly associated with a higher rate of clinical pregnancies (p: 0.003, OR: 4.9, 95% CI: 1.7–14.2). The pregnancy rate was also significantly increased by the use of LMWH alone (p: 0.005, OR: 2.6, 95% CI: 1.3–5.0). Carriership of inherited or acquired thrombophilia did not affect clinical outcomes of the ART. The efficacy of antithrombotic treatment was confirmed when the outcome “ live-birth” was considered. Present data suggest a potential benefit of antithrombotic prophylaxis during ART in improving the number of live-births.

Venous thromboembolism in assisted reproductive technologies: comparison between unsuccessful versus successful cycles in an Italian cohort

Pregnancies after assisted reproductive technologies (ART) have been associated with an increased risk of venous thromboembolism (VTE). On the contrary, the magnitude of this risk in unsuccessful ART cycles (not resulting in a clinical pregnancy) has not yet been clearly defined. In this study, we evaluated the incidence of VTE in unsuccessful cycles and compared it with that recorded in successful cycles in the same study population. From a cohort of 998 women consecutively referred by local Fertility Clinics to our Atherosclerosis and Thrombosis Unit (April 2002–July 2011), we identified and included women with at least one cycle of ovarian stimulation and a negative history for VTE. Overall, 661 women undergone 1518 unsuccessful and 318 successful cycles of ovarian stimulation, respectively, were analysed. VTE events occurred in 2/1518 (1.3‰) unsuccessful cycles compared with 3/318 (9.4‰) successful cycles, (Two-tailed Fisher exact test, p = 0.04, OR 0.14, 95% CI 0.02–1.02). Both cases observed in unsuccessful cycles were isolated pulmonary embolism occurred after OHSS; no antithrombotic prophylaxis had been prescribed. At logistic regression analysis, the occurrence of successful cycle and BMI were significantly and independently associated with the occurrence of VTE with an OR of 13.94 (95% CI 1.41–137.45) and 1.23 (95% CI 1.01–1.49), respectively. VTE incidence is significantly lower in unsuccessful cycles as compared to that of successful ones. However, although rare, thrombotic risk during ovarian stimulation cannot be excluded and, when it occurs, can be life-threatening. Therefore, particular attention should be paid to these women, independently of ART outcome.

FGM in Switzerland: between legality and loyalty in the transmission of a traditional practice

ABSTRACT Excision and infibulations, otherwise known as ‘female genital mutilation (FGM)’, is recognised internationally as a violation of the human rights of girls and women. The population affected by FGM in Switzerland is young and characterised by a first-generation migratory background. It is estimated around 14,700 women affected by excision or infibulation live in Switzerland. In 2012, a specific law against FGM was approved and the Criminal Code amended to include excision or infibulation as a crime (article 124), testifying to the Swiss government’s strong political commitment to eliminating FGM. Our study looked into this political context and the current public policy agenda with the aim to better understand the specific logic of the intergenerational transmission of FGM. In particular, this article discusses the reasons invoked by women concerning such a transmission, their attitudes about the new generation of daughters and their demands on what it is possible to do, in the present, to recover and to go forward after FGM.

Prior Uterine Evacuation and the Risk of Short Cervical Length: A Retrospective Cohort Study: Prior Uterine Evacuation and Risk of a Short Cervix

To determine whether a prior uterine evacuation procedure is associated with an increased risk of short cervical length (≤20 mm) in women without prior spontaneous preterm birth.

Decrease in the incidence of threatened preterm labor after implementation of transvaginal ultrasound cervical length universal screening

Abstract Background: It is unknown if universal second-trimester transvaginal ultrasound (TVU) cervical length (CL) screening in asymptomatic women with singleton gestations and no prior spontaneous preterm birth (SPTB) affects the incidence of symptoms of preterm labor (PTL) later in pregnancy. Objective: To evaluate the incidence of threatened PTL before and after the implementation of universal second trimester TVU CL screening. Study design: This was a retrospective cohort study of all consecutive singleton gestations without prior SPTB presenting to obstetric triage for threatened PTL between 23 0/7 and 33 6/7 week in 2011 (1 January–31 December), and in 2014 (1 January–31 December) at Thomas Jefferson University Hospital (TJU) (Philadelphia, PA). These 2 years were chosen as a new protocol for universal TVU CL screening was started on 1 January 2012. This protocol involved one measurement of TVU CL in all singleton gestations without a prior SPTB at 18 0/7 − 23 6/7 week, the time of the “anatomy” scan. Women with prior SPTB were excluded from this study. The primary outcome included the incidence of threatened PTL, defined as the number of women with singleton gestations without prior SPTB who presented with threatened PTL to our labor and delivery (L&D) triage unit annually, divided by the total number of annual deliveries of women with singleton gestation without prior SPTB. Secondary outcomes were the incidence of PTL, defined as the number of women with singleton gestations without prior SPTB admitted for PTL annually divided by the total number of annual deliveries of women with singleton gestation and without prior SPTB; and length of stay in the hospital. We aimed to compare primary and secondary outcome in the “2011” versus the “2014” group. Results: In 2011, there were a total of 1745 deliveries at TJU, of which 1550 (88.8%) were singletons without prior SPTB. In 2014, there were a total of 1924 deliveries at TJU, 1751 (91.0%) were singletons without prior SPTB who were offered universal TVU CL screening. One hundred and seventy-two women with singletons without prior SPTB presented in L&D triage unit in 2011; and 118 women with singletons without prior SPTB presented in L&D triage unit in 2014. There were significant decreases in the incidence of threatened PTL from 11.1% (172/1550) in 2011 to 6.7% (118/1751) in 2014 (p < .001), as well as in the rate of admission for PTL from 2.3% (35/1550) to 1.4% (24/1751), respectively (p = .04). Length of stay was not significantly different between the two groups. Conclusion: The introduction of a universal TVU CL screening program in women with singleton gestations without a history of SPTB is associated with a reduction in the frequency of threatened PTL and admission for PTL. Key Message The introduction of a second trimester universal transvaginal ultrasound (TVU) cervical length (CL) screening program in women without a history of spontaneous preterm birth (SPTB) is associated with a reduction in the incidence of threatened preterm labor (PTL) and admission for PTL.