Increased incidence of preeclampsia in mothers of advanced age conceiving by oocyte donation.

PURPOSE: The aim of this study was to evaluate the risk of preeclampsia in women of advanced age who conceived through donated oocytes as compared with natural conceptions. METHODS: A historical prospective study of singleton live births of parturients ≥ 45 years of age at four university hospitals was conducted. For the purpose of the study, the population was divided by the mode of conception into two groups: oocyte donation and natural conception. The main outcome variable in this study was preeclampsia. Secondary outcomes included pregnancy-induced hypertension and Small for Gestational Age. RESULTS: Two hundred and seventy pregnancies were achieved naturally and 135 women conceived by oocyte donation. Mean age at delivery for the natural conception and oocyte donation groups was 45.7 and 47.8, respectively. Preeclampsia complicated 3 out of 270 (1.1%) natural conception pregnancies and 17 out of 135 (12.6%) oocyte donation conceptions. After adjusting for confounders, oocyte donation pregnancies were found to be associated with a 12-fold increased risk for preeclampsia (P = 0.001). Among oocyte donation pregnancies, the risk of preeclampsia was not affected by parity or age. CONCLUSIONS: A substantially increased risk for preeclampsia was found in oocyte donation pregnancies, suggesting that the foreign oocyte may play a specific biologic role in the development of preeclampsia after the age of 45.

The effects of maternal age and parity on maternal and neonatal outcome.

PURPOSE: Delayed childbearing is increasingly common; hence, concerns emerge regarding potential for additional risks of delivery at advanced maternal age (AMA; ≥35 years). In this study, we sought to assess impact of AMA and parity on maternal and perinatal outcomes. METHODS: In this retrospective single-center study (July 2005 to October 2011), we compared spontaneously-conceived singleton births of AMA mothers with spontaneously-conceived singletons of mothers aged 24-27 years. Maternal outcomes: incidence of diabetes, hypertension, and emergency cesarean sections (ECS). Neonatal outcomes: prematurity, birth weight, incidence of small or large for gestational age infants (SGA/LGA, respectively), low birth weight (LBW), and 5'-Apgar scores. Sub-groupings of maternal age were 35-38, 39-42, or 43-47 years; prematurity as <34 or <37 weeks; AMA parity as primiparous, 2-5 births, 6-9 births, or ≥10 births. Binary logistic regression was used for multivariate analyses. RESULTS: Of 24,579 eligible women, 11,243 were AMA (14.0% total singleton births) and 13,336 were aged 24-27 years (16.7% total singleton births) at delivery. There were no maternal or perinatal deaths. Incidence of maternal hypertension and diabetes was significantly greater in AMA, especially oldest AMA. AMA including primiparous had significantly more ECS than younger including primiparous controls, respectively, and were more likely to deliver LGA neonates. Primiparous AMA women did not have increased incidence of LGA babies but significantly increased incidence of SGA infants. CONCLUSION: AMA, especially primiparous, has more adverse maternal and neonatal outcomes than younger women; however, these did not include mortality. Consistent antenatal care may explain this.

Outcome of pregnancies in women receiving velaglucerase alfa for Gaucher disease.

AIM: Pregnancy and delivery are affected by and - in turn - impact signs and symptoms of Gaucher disease (GD). Prior to enzyme replacement therapy (ERT), the reported missed abortions rate was 25%, with worsening of anemia and thrombocytopenia, with increased frequency of post-partum hemorrhage, puerperal fever and bone crises during pregnancy. ERT with imiglucerase reduced these adverse events. Velaglucerase alfa (VPRIV), an ERT approved commercially in February 2010, had undergone preclinical reproductive toxicity testing and proven to be safe and effective in phase I/II and III clinical trials. The objective of this study was to ascertain pregnancy outcome in women receiving VPRIV. METHODS: Among records collected from six multinational clinical sites, 21 females (mean age, 32.0 years) with GD received VPRIV. RESULTS: There were 25 singleton pregnancies (mean gravidity, 2.7; mean parity, 2.0; mean months VPRIV, 31.2). Two primiparous women suffered three first trimester abortions and one missed abortion occurred in a multigravida female. Live birth rate was 84% (mean gestational age, 39.7 weeks). Mean birthweight was 3234.4 g, with APGAR scores above 9. All but three were vaginal deliveries; elective cesarean sections were performed in two patients with hip arthroplasty and one after previous cesarean. Nine patients received regional analgesia/anesthesia. Post-partum complications were rare, with only one post-partum (placental) bleed which resolved without intervention. Mean hemoglobin and platelet counts improved during pregnancy (9.45% and 26.0%, respectively). CONCLUSION: VPRIV is safe for conception and pregnancy with good maternal and neonatal outcomes.

The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause).

BACKGROUND: The principal manifestations of type 1 Gaucher disease (GD) (increased risk of bleeding, anaemia, splenomegaly, hepatomegaly and bone disease) are likely to affect females during reproductive events such as menarche and menstruation; fertility, pregnancy, parity, delivery and lactation; and menopause. In order to determine the optimal management of female Gaucher patients based on available data, we examine reproductive events and GD in untreated and alglucerase and/or imiglucerase-treated females. METHODS: A panel of international clinicians experienced in the management of GD reviewed and presented evidence from peer-reviewed literature, a pharmacovigilance database on imiglucerase, and their own clinical experience to support discussions and recommendations. Nine panel members completed a 130-item-questionnaire on the outcomes of the management of female patients in their clinical practice. Results, covering menarche (137 females), menstruation (261 reports), fertility (295 females), pregnancy (416 pregnancies in 247 women) and menopause (45 women) were analysed. Data from a recent Canadian survey on 50 patients with 39 pregnancies, the imiglucerase pharmacovigilance database (100 pregnancies), and relevant literature (56 items covering 398 pregnancies in 205 women) were also reviewed. KEY RESULTS: Menarche: May be delayed in girls with GD. Menorrhagia: Appears to be more common in GD than in the non-Gaucher population and may be ameliorated by alglucerase and/or imiglucerase treatment (menorrhagia in 67/133 (50.4%) untreated females compared with 37/128 (28.9%) treated; Mann-Whitney U test: p=0.001). Fertility: There is no evidence of decreased fertility in GD. Pregnancy: Pregnancy in GD may be complicated by haematological disease, organomegaly and bone involvement. GD diagnosis occurs frequently during pregnancy. Questionnaire results demonstrate: a reduced risk of spontaneous abortion in women treated with alglucerase and/or imiglucerase (untreated: 26/189 (13.8%); treated 1/58 (1.7%) chi(2)p=0.010); reduced risk of Gaucher-related complications during delivery (untreated 43/109 (39.4%); treated 3/46 (6.5%) chi(2)p<0.0005): and a reduced risk of Gaucher-related complications during the post partum period (untreated 15/71 (21.1%); treated 3/43 (7%) chi(2)p=0.014). There is no evidence to date of any untoward effect of alglucerase and/or imiglucerase on the fetus, or on infants breast fed by mothers receiving alglucerase and/or imiglucerase. Menopause: The impact of GD on menopause requires further study especially in relation to bone pathology. CONCLUSIONS: On the basis of this review, GD may have an impact on reproductive events in affected women. Enzyme therapy may have benefits in reducing menorrhagia, spontaneous abortions and complications associated with delivery and the postpartum period.

Effect of thrombocytopenia on mode of analgesia/anesthesia and maternal and neonatal outcomes.

OBJECTIVES: The purpose was to correlate the use of regional analgesia/anasthesia among women with different degrees of thrombocytopenia relative to women with normal platelet counts, and note maternal and neonatal outcome, and mode of delivery. METHODS: A case-control paradigm was developed based on women who delivered during 2007-2011 with platelet counts ≤80 000/mm(3). For each woman in this "severe" thrombocytopenic group, an age- and parity-matched control was found who delivered a singleton within the same year but whose platelets were either 81 000-150 000/mm(3) ("moderate" thrombocytopenia) or ≥151 000/mm(3) (normal platelet counts). RESULTS: 168 women were identified for each group; mean maternal age (28.4 years), mean gravidity (4.3), mean parity (3.7), mean gestational age (39.2 weeks) and mean birth weight (3283 g) were comparable. However, only in the severe thrombocytopenic women were there very early preterm deliveries, lowest birth weight, lowest Apgar scores, the greatest number with serious post-partum hemorrhage (>500 ml); use of regional analgesia/anesthesia was lowest, and percent cesarean sections highest. CONCLUSIONS: This study highlights potential for adverse maternal outcome of post-partum hemorrhage and adverse neonatal outcomes of prematurity, low birth weight, and low Apgar scores (but not neonatal death), and limited regional analgesia/anesthesia in women who present at delivery with severe (≤80 000/mm(3)) thrombocytopenia.

The management of pregnancy in Gaucher disease.

Gaucher disease (GD), characterized by deficient acid ß-glucosidase activity, is the most common lysosomal storage disorder. The disease is progressive with manifestations that include anemia, thrombocytopenia, organomegaly and bone disease. Pregnancy has the potential to exacerbate these manifestations, compounding the risk of complications during pregnancy, delivery and postpartum. Enzyme replacement therapy with imiglucerase, before and during pregnancy, has demonstrated benefits in reducing the risk of spontaneous abortion and GD-related complications, especially bleeding during delivery and postpartum. European Medicines Agency guidelines now indicate that treatment-naive women should be advised to consider imiglucerase therapy before conception to obtain optimal health, and that imiglucerase treatment should be considered throughout pregnancy for women already receiving therapy. Many questions remain, however, on the indications for treatment and optimal management of women with GD. Based on a comprehensive review of outcomes in the management of pregnancy in GD, we present recommendations that aim to optimize patient care around pregnancy, delivery and the postpartum period, and alert attending physicians to the possible complications of pregnancy and delivery in GD.

The pattern of Protease Activated Receptor 1 (PAR1) expression in endometrial carcinoma.

OBJECTIVE: Protease Activated Receptors (PARs) form a family of G-protein-coupled proteins uniquely activated by proteolytic cleavage. While the role of either soluble or matrix-immobilized protease in tumor invasion is well established, the part of cell surface PARs is beginning to emerge. We sought to investigate the expression pattern of Protease Activated Receptor 1 (hPar1) in endometrial carcinoma, the most common type of gynecological malignancy. METHODS: Tissue biopsy specimens taken from seventy-four formalin-fixed, paraffin-embedded endometrial tissue blocks were obtained from archival material. Analysis of PAR1 expression was evaluated by riboprobe in situ hybridization for detection of RNA and immunohistochemistry techniques for localization of protein. Histological scoring was performed. RESULTS: The levels of hPar1 mRNA and protein were high and abundant in high-grade endometrial carcinoma, regardless of the histological subtype. In contrast, no hPar1 was detected in endometrial epithelia with conserved glandular structure represented by normal, hyperplastic or low-grade carcinomas. CONCLUSIONS: PAR1 over-expression is selectively confined to the highly aggressive, high-grade endometrial carcinoma and absent in tissue obtained from benign endometrium or low-grade endometrial cancer. This finding highlights the significance of hPar1 gene involvement in invasive endometrial carcinoma and appoints it an attractive candidate for anti-cancer therapy.

Pregnancies in Gaucher disease: a 5-year study.

OBJECTIVE: The study was undertaken to investigate the outcome of pregnancies in Gaucher disease, particularly in enzyme-treated women. STUDY DESIGN: A retrospective study was performed of pregnant women evaluated at a referral clinic. RESULTS: There were 43 (17 treated, 26 untreated) women with 66 pregnancies (23 treated, 43 untreated). The live birth rate was 78.3% among treated, 86.0% among untreated. One treated woman had three spontaneous abortions; 3 untreated women had one each. Four pregnancies in each group had postpartum bleeding, 7 requiring transfusions. Postpartum infections were prevalent among treated. Cesarean sections were generally for historic reasons. There was no exacerbation of Gaucher disease, except one bone crisis. CONCLUSION: Most untreated women with milder disease enjoyed an uncomplicated course. Enzyme-treated patients (ie, with more severe disease) had more bleeding and infections post partum, but few had spontaneous abortions. Hematologic consultation is recommended. A review of world experience with pregnant patients with Gaucher disease is included.