Endometriosis is associated with a decreased risk of pre-eclampsia

BACKGROUND: 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.     

Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy

BACKGROUND: We prospectively assessed growth and motor-social development during the first 18 months of life in 126 live births (122 pregnancies) to 109 women with polycystic ovary syndrome (PCOS) who conceived on and continued metformin (1.5-2.55 g/day) through pregnancy. METHODS: The lengths and weights of PCOS neonates were compared with gender-specific Centers for Disease Control and Prevention (CDC) infant data. Gestational diabetes (GD) and pre-eclampsia in women with PCOS were compared with 252 healthy women without PCOS who had >or=1 live birth (262 live births). RESULTS: There were 101 out of 126 (80%) term (>or=37 gestational weeks) PCOS births, which was not significantly different (P = 0.7) from controls, 206 out of 252 (81.7%). There were two (1.6%) birth defects. GD occurred in nine out of 119 PCOS pregnancies (7.6%) versus 40 out of 251 (15.9%) controls, P = 0.027. The prevalence of pre-eclampsia did not differ in PCOS versus control pregnancies (4.1 versus 3.6%, P = 0.8). The birth length and weight of the 52 male neonates did not differ (P > 0.05) from those of CDC males; the 74 female neonates were shorter than CDC females (48.9 +/- 5.4 versus 50.6 +/- 2.7 cm, P = 0.006) and weighed less (3.09 +/- 0.85 versus 3.29 +/- 0.52 kg, P = 0.04). There were no systematic differences in growth between PCOS and CDC infants over 18 months. At 3, 6, 9, 12 and 18 months, of a potential 100% motor-social development score, scores (+/-SD) were 95 +/- 13, 98 +/- 8%, 95 +/- 10, 97 +/- 8 and 94 +/- 16%; no infants had motor-social developmental delays. CONCLUSIONS: Metformin reduced development of GD, was not teratogenic and did not adversely affect birth length and weight, growth or motor-social development in the first 18 months of life.     

Prevalence of cervical insufficiency in polycystic ovarian syndrome

BACKGROUND Pregnant women with polycystic ovarian syndrome (PCOS) experience a greater rate of adverse obstetrical outcomes compared with non-PCOS women. We examined the prevalence and incidence of cervical insufficiency (CI) in a community cohort of pregnant women with and without PCOS. METHODS A retrospective cohort study was conducted within a large integrated health care delivery system among non-diabetic PCOS women with second or third trimester delivery during 2002-2005 (singleton or twin gestation). PCOS was defined by Rotterdam criteria. A non-PCOS comparison group matched for delivery year and hospital facility was used to estimate the background rate of CI. Women were designated as having new CI diagnosed in the index pregnancy (based on cervical dilation and/or cervical shortening) and prior CI based on prior diagnosis of CI with prophylactic cerclage placed in the subsequent pregnancy. RESULTS We identified 999 PCOS women, of whom 29 (2.9%) had CI. There were 18 patients with new CI and 11 with prior CI having prophylactic cerclage placement; four CI patients had twin gestation. In contrast, only five (0.5%) non-PCOS women had CI: two with new CI and three with prior CI. The proportion of newly diagnosed incident CI (1.8 versus 0.2%) or prevalent CI (2.9 versus 0.5%) was significantly greater for PCOS compared with non-PCOS pregnant women (both P < 0.01). Among PCOS women, CI prevalence was particularly high among South Asians (7.8%) and Blacks (17.5%) compared with Whites (1%) and significantly associated with gonadotropin use (including in vitro fertilization). Overall, the PCOS status was associated with an increased odds of prevalent CI pregnancy (adjusted odds ratio 4.8, 95% confidence interval 1.5-15.4), even after adjusting for maternal age, nulliparity, race/ethnicity, body mass index and fertility treatment. CONCLUSION In this large and ethnically diverse PCOS cohort, we found that CI occurred with a higher than expected frequency in PCOS women, particularly among South Asian and Black women. PCOS women with CI were also more likely to have received gonadotropin therapy. Future studies should examine whether natural and hormone-altered PCOS is a risk factor for CI, the role of race/ethnicity, fertility drugs and consideration for heightened mid-trimester surveillance in higher risk subgroups of pregnant women with PCOS.     

Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment.

BACKGROUND: A high proportion of infertile patients have polycystic ovarian syndrome (PCOS) with a reportedly greater risk of spontaneous abortion. Because of the close link between PCOS and obesity and the independent association of obesity with poor pregnancy outcomes, it is important to distinguish the possible confounding effect of body mass index (BMI) or other variables from that of PCOS. This study aims to determine the effect of PCOS status on the risk of spontaneous abortion with adjustment for body mass and several other confounding factors in a large cohort of pregnant infertile women. METHODS: The patients (n = 1018) were treated in a tertiary infertility centre. Their PCOS status was determined by standard criteria and their BMI had been taken less than 1 year before the pregnancy. Patients whose PCOS status or BMI measurements were not assessed were excluded. Student's t-test or chi2 test were used to test the difference between the PCOS and non-PCOS groups while a multivariate logistical regression model was used to assess the effect of PCOS, BMI and other confounding factors. RESULTS: Overall, the incidence of PCOS was 37% in this cohort. The overall incidence of spontaneous abortion in the study population was 21%. Univariate analysis showed that women with PCOS had a significantly greater risk of spontaneous abortion compared with non-PCOS women (25 versus 18%, P < 0.01). However, using multivariate logistic regression analysis this effect was reduced to a non-significant level [odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.85-1.36] after adjusting for obesity and patients/treatment combination factor, and to nil after adjusting for all confounding factors considered in this study (OR = 0.98, 95% CI 0.75-1.28). CONCLUSION: The results of this study suggest that the higher risk of spontaneous abortion observed in women with PCOS is likely to be due to their high prevalence of obesity and the type of treatment they receive.     

Survival rates during the first trimester of multiple gestations achieved by ICSI: a report of 1448 consecutive multiples

BACKGROUND: The purpose of this study was to determine the rate of spontaneous gestational sac loss during the first trimester in women achieving multiple pregnancies by ICSI. METHODS: A retrospective analysis was performed of 1448 consecutive multiple pregnancies conceived by ICSI. RESULTS: Of the cohort of 1448 pregnancies, twin gestations constituted 59.6% (864), triplets 30.2% (438) and quadruplets 10.0% (146). During the first trimester, 69 (4.7%) patients miscarried, while 179 (12.3%) continued their pregnancies and had fewer gestational sacs at the end of the first trimester than at the beginning. The overall loss rate of any gestational sac during the first trimester in these multiple pregnancies was 10.1%. There was a significant difference in the frequency of spontaneous reduction to twin or singleton pregnancies in the first trimester between women carrying triplets (11.7%) and those carrying quadruplets (3.5%) [P = 0.004; odds ratio (OR) 3.5; 95% confidence interval (CI) 1.3-9.1]. The frequency of gestational sac loss was significantly greater among women >35 years old (20.9%) than in women less than 35 years old (15.9%) (P = 0.03; OR 1.4; 95% CI 1.0-1.9). CONCLUSION: In multiple pregnancies there is a significant risk of spontaneous loss of any embryo during the first trimester. These findings should be considered prior to any decision about selective embryo reduction.     

A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.     

Perinatal and obstetric outcomes of donor insemination using cryopreserved semen in Victoria, Australia.

This study compared the perinatal and obstetric outcomes of 1552 donor insemination pregnancies in Victoria, Australia, with a control group of 7717 normally conceived pregnancies from the general population. Data on the outcomes of pregnancies of at least 20 weeks gestation, for both groups, were obtained from the same population-based birth registry. The study showed that there were no significant differences between the donor insemination and control groups in the incidence of preterm birth, low birthweight, multiple birth, perinatal death and birth defects, or in the sex ratio. Pregnancies conceived by donor insemination were significantly more likely than controls to have an induced labour (OR = 1.6, 95% CI 1. 4-1.8), a forceps delivery (OR = 1.5, 95% CI 1.3-1.8) and/or a Caesarean section (OR = 1.6, 95% CI 1.4-1.9) and to develop pre-eclampsia (OR = 1.4, 95% CI 1.2-1.8) after adjusting for maternal age, multiple birth, parity and presentation. Reasons for the higher rate of induced and operative deliveries are not clear. Overall, the study's findings are reassuring for couples considering infertility treatment with donor insemination. The study illustrates the importance of complete follow-up in studies of pregnancy outcomes after assisted conception and the use of appropriate population-based control groups with comparable ascertainment of outcomes.     

妊娠期糖尿病相关危险因素分析

目的 探讨妊娠期糖尿病相关的危险因素。方法 收集2012年10月~2014年2月在中山大学附属第三医院产检并住院分娩的483例GDM患者和327例非GDM患者的临床资料,并对其临床资料进行单因素和多因素统计分析。结果 早期空腹血糖（10~22 周）、文化程度、中孕期甘油三脂、孕前BMI指数、年龄和孕期体重增加比较中,GDM组和非GDM组数据差异有统计学意义（P均＜0.05）,多因素分析显示早期空腹血糖（10~22周）[OR=2.380,95%CI 1.409~4.021,P=0.001]、文化程度[OR=1.775,95%CI 1.082~2.909,P=0.023]、中孕期甘油三脂[OR=1.295,95%CI1.081~1.551,P=0.005]、孕前BMI[OR=1.146,95%CI1.053~1.247,P=0.002]和年龄[OR=1.113,95%CI 1.050~1.181,P=0.001]是GDM临床相关危险因素。结论 早期空腹血糖（10~22周）、文化程度、中孕期甘油三脂、孕前BMI、年龄是GDM的危险因素。     

PCOS患者不良妊娠结局的相关因素分析

目的 探讨多囊卵巢综合征(PCOS)患者不良妊娠结局的相关因素.方法 回顾性分析我院2009年1月至2017年1月收治的82例PCOS患者的临床资料及妊娠结局,根据妊娠结局分组,比较各组临床资料,且通过Logistic多因素回归分析影响PCOS患者妊娠结局的危险因素.结果 不良妊娠结局发生率15.85％;不良妊娠结局组与非不良妊娠结局组在体重指数(BMI)≥25kg/m2、腰臀比≥0.8、妊娠期糖尿病(GDM)发生率、血清卵泡刺激素(FSH)、黄体生成素(LH)、总睾酮(T)、性激素结合蛋白(SHBG)、空腹胰岛素(INS)、游离睾酮指数(FTI)上比较差异均有统计学意义(P＜0.05);Logistic多因素回归分析显示PCOS患者不良妊娠结局发生的危险因素包括BMI、腰臀比、GDM、INS、FTI,保护因子为SHBG(均P＜0.05).结论 PCOS不良妊娠结局主要包括早产、流产等,其发生与患者高BMI、大腰臀比、GDM、FTI等密切相关,需根据相关因素积极纠正,以改善患者妊娠结局.     

The PON1-108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women

BACKGROUND: Because serum paraoxonase activity is influenced by the -108C/T polymorphism in the PON1 gene, we studied its involvement in the decreased paraoxonase activity recently described in the polycystic ovary syndrome (PCOS). METHODS: Paraoxonase activity, PON1-108C/T genotypes and clinical, hormonal and biochemical variables were evaluated in a case-control study involving 139 consecutive PCOS patients and 85 healthy controls matched for BMI and prevalence of smoking. RESULTS: Women homozygous for -108T presented with reduced serum paraoxonase activity compared with carriers of C alleles (P < 0.001), both in PCOS patients and in controls. Although homozygosity for T alleles was more prevalent in PCOS patients than in controls (P = 0.003), serum paraoxonase activity was not significantly different in the PCOS and control groups. In a stepwise multivariate linear regression model, homozygosity for PON1-108T alleles was the only significant predictor of the logarithm of serum paraoxonase activity (beta = -0.328, t = -4.176, P < 0.001). CONCLUSIONS: In premenopausal women from the Spanish population, the PON1-108C/T polymorphism, and not PCOS, is an important determinant of serum paraoxonase activity.     

Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood

BACKGROUND: To compare first-time parenthood probability and pregnancy outcome between cancer patients and the general population. METHODS: Data from a hospital registry on cancer patients aged 15-35 years at diagnosis, including date/type of diagnosis, treatment and date of death, were merged with data from the Cancer Registry and the Medical Birth Registry, providing date of childbirth, IVF, pregnancy outcomes and demographics. RESULTS: The first-time parenthood probability at the age of 35 years was 63% in male patients (n = 463) and 64% in the male general population (n = 367 068). Figures in female patients were 66% (n = 284) compared with 79% in the female general population (n = 349 576) (P = 0.007). A total of 487 male and 251 female cancer patients were childless pre-diagnosis, and 130 male and 104 female cancer patients had one child before diagnosis and at least one birth post-diagnosis. Congenital anomalies were more frequent in first-borns to previously childless male patients [adjusted odds ratio (OR(adj)): 1.5; 95% confidence interval (CI): 1.1-2.3]. The risk of low birth weight and preterm delivery after cancer was increased in infants born to female patients, as was perinatal mortality (OR(adj) 2.3; 95% CI: 1.1-5.0) among post-diagnosis first births. CONCLUSIONS: The first-time parenthood probability in 35-year old cancer patients is approximately 60%, which in female patients is significantly reduced compared with the general population. Post-diagnosis pregnancies to female patients are high-risk pregnancies.     

Effects of subfertility cause, smoking and body weight on the success rate of IVF

BACKGROUND: We investigated the separate and combined effects of smoking and body mass index (BMI) on the success rate of IVF for couples with different causes of subfertility. METHODS: The success rate of IVF was examined in 8457 women. Detailed information on reproduction and lifestyle factors was combined with medical record data on IVF treatment. All IVF clinics in The Netherlands participated in this study. The main outcome measures were live birth rate per first cycle of IVF differentiated for the major predictive factors. RESULTS: For male subfertility the delivery rate per cycle was significantly lower than unexplained subfertility, OR of 0.70 (95% CI 0.57-0.86); for tubal pathology, the delivery rate was slightly lower, OR = 0.86 (95% CI 0.70-1.01). Smoking was associated with a significantly lower delivery rate was slightly lower; for OR = 0.72 (95% CI 0.61-0.84) and a significantly higher abortion rate compared to non-smoking delivery rates of 21.4% and 16.4%, respectively (P=0.02). Women with a BMI of > or = 27 kg/m2 had a significantly lower delivery rate, with an OR of 0.67 (95% CI 0.48-0.94), compared with normal weight women (BMI > or = 20 and <27 kg/m2). CONCLUSIONS: Both smoking and overweight unfavourably affect the live birth rate after IVF. The devastating impact of smoking on the live birth rate in IVF treatment is comparable with an increase in female age of >10 years from age 20 to 30 years. Subfertile couples may improve the outcome of IVF treatment by lifestyle changes.     

Serum adiponectin and lipid concentrations in pregnant women with polycystic ovary syndrome

BACKGROUND: We aimed to evaluate the serum adiponectin and lipid concentrations in normal and polycystic ovary syndrome (PCOS) women during pregnancy in order to establish whether PCOS induces abnormal lipid and adiponectin levels that could constitute potential metabolic risk factors for pregnancy complications. METHODS: Women with singleton pregnancies and of similar age were included (48 pregnant PCOS and 51 normal pregnant women). During gestational weeks 10-16 and 22-28, a 2 h, 75 g oral glucose tolerance test was performed, with measurement of glucose and insulin in each sample. Adiponectin and lipid concentrations were determined in the fasting sample. RESULTS: The incidence of gestational diabetes mellitus (GDM) was significantly higher in the PCOS group (12.2%) compared with the control group (2%). In PCOS patients, triglyceride (TG) concentrations and area under the curve of glucose and insulin were higher in both study periods and adiponectin concentrations were significantly lower in the second period, compared with normal women. Moreover, adiponectin concentrations were lower in women with GDM than in those with normal glucose tolerance in the two study periods. CONCLUSION: Low adiponectin and high insulin levels are associated with GDM in pregnant PCOS patients. High TG levels seem not to be directly related to pregnancy complications in these patients.     

Obstetric outcome after prenatal diagnosis in pregnancies obtained after intracytoplasmic sperm injection

In this study we compared the pregnancy outcome of 576 pregnanciesafter prenatal diagnosis with that of 540 pregnancies withoutprenatal diagnosis in our micro-injection programme. Amniocentesiswas suggested for singleton pregnancies (n = 465) and chorionicvillus sampling (CVS) was proposed for twin pregnancies (n =111 pregnancies, 222 fetuses). A total of 365 patients withsingleton pregnancies and 175 patients with twin pregnancieswho did not undergo prenatal diagnosis were selected as controls.Compared with the controls, the odds ratios in the amniocentesisgroup for preterm delivery, low birthweight, very low birthweightand fetal loss were 0.97 [95% confidence interval (CI): 0.60–1.57],1.27 (95% CI: 0.78–2.06), 1.57 (95% CI: 0.53–4.66)and 0.86 (95% CI: 0.32–2.37) respectively. Compared withthe controls, the odds ratios in the CVS group for preterm delivery,low birthweight, very low birthweight and fetal loss were 0.89(95% CI: 0.61–1.30), 1.03 (95% CI: 0.74–1.45), 0.79(95% CI: 0.41–1.53) and 0.47 (95% CI: 0.17–1.30)respectively. We concluded that, in this series of intracytoplasmicsperm injection (ICSI) pregnancies, prenatal testing did notincrease the preterm-delivery, the low-birthweight, or the verylow-birthweight rates as compared with those of the controls.In the prenatal diagnosis group, the fetal loss rate was comparableto that of the control group. Larger prospective controlledstudies are needed in order to inform patients reliably aboutthe risks and the advantages of prenatal testing in ICSI pregnancies.     

Pregnancy outcome in women with PCOS and in controls matched by age and weight

BACKGROUND: The aim of this study was to compare the pregnancy outcome, especially the prevalence of gestational diabetes mellitus (GDM), in a group of patients with polycystic ovary syndrome (PCOS), with a group of healthy weight-matched women. METHODS: Retrospectively, we evaluated the pregnancies of 66 women with PCOS, who had been treated for infertility and who delivered at our department. These were compared with a group of 66 age- and weight-matched controls. RESULTS: We did not find any significant differences in the prevalence of pregnancy complications such as gestational diabetes mellitus, pregnancy-induced hypertension (PIH) and premature deliveries between the group of PCOS patients and the controls. CONCLUSION: When differences in age and weight between PCOS patients and controls are negligible, PCOS is not associated with a higher risk of pregnancy complications.     

瘦素及瘦素受体基因多态性与重度子痫前期发病的相关性

目的 探讨血清瘦素水平和瘦素受体基因(leptin receptor gene,LEPR)Pro1019Pro (G1019A)和Gln223Arg(A223G)多态性与重度子痫前期发病的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法检测207例重度子痫前期和252名正常妊娠孕妇(对照组)LEPR基因G1019A和A223G多态性;ELISA法检测血清瘦素水平.结果 (1)重度子痫前期组患者血清瘦素水平显著高于正常对照组孕妇,新生儿体重明显低于对照组,早产儿发生率显著高于对照组(P＜0.01).(2) LEPR基因G1019A多态性GA基因型和G等位基因频率重度子痫前期组(33.8％和20.3％)显著高于对照组(19.8％和15.1％)(P＜0.01),携带GA型和G等位基因孕妇发生重度子病前期的风险较AA型和A等位基因个体分别增加2.04倍(95％CI:0.77～5.42)和1.43倍(95％CI:1.02～2.01).(3)LEPR基因A223G多态性AG基因型和A等位基因频率分布重度子痫前期组(19.3％和12.6％)明显低于对照组(34.5％和19.2％)(P＜0.01),携带AG型和A等位基因孕妇发生重度子痫前期的风险较GG型和G等位基因个体分别降低0.46倍(95％CI:0.30～0.71)和0.60倍(95％ CI:0.42～0.87).(4)LEPR G1019A和A223G多态性“1019AA+223AG”联合基因型频率重度子痫组(6.8％)显著低于对照组(24.6％)(P＜0.01),携带者发生重度子痫前期的风险较其它联合基因型个体低0.22倍,95％CI:0.12～0.39;而“1019GA+223GG”联合基因型频率重度子痫前期组(22.2％)显著高于对照组(11.9％)(P＜0.05),携带者发生重度子病前期的风险增加2.10倍,95％CI:0.78～3.45.(5)LEPR基因G1019A和A223G多态性各基因型之间收缩压、舒张压、体重指数和血清瘦素水平比较差异均无统计学意义(P＞0.05).结论 血清中高浓度的瘦素水平和LEPR基因G1019A、A223G多态性与重度子痫前期发病可能存在关联,血清瘦素水平与LEPR基因G1019A和A223G多态性无关;G1019A GA基因型和“1019GA+ 223GG”联合基因型可能是重度子痫前期的易感基因型.     

Birth weight in pre-eclamptic and normotensive twin pregnancies: an analysis of discordance and growth restriction

The aim of this study was to verify whether twin pregnancies complicated by pre-eclampsia were associated with a higher rate of inter-twin weight discordance or an increased prevalence of small for gestational age (SGA) neonates than in normotensive twin pregnancies. A 17 year retrospective study was undertaken by examining 76 twin pregnancies complicated by pre-eclampsia and comparing them with 400 normotensive twin pregnancies. The case notes were reviewed in reference to birth weight differences, birth order, pregnancy outcome and inter-twin birth weight discordance. Statistical analyses were performed with t-test, contingency tables, regression curves, rank sum test and non-parametric survival plots. Power analysis was also carried out. Pre-eclamptic twin pregnancies were delivered at similar weeks of gestation to normotensive. They resulted in a smaller size for the second twin the earlier the delivery week, while in normotensive twin pregnancies no significant difference occurred at any week. Twin pregnancies complicated by pre-eclampsia showed higher rates of SGA neonates among second twins than those with normal pressure. The >25% discordance was associated with lower gestational age at delivery in each group [mean (range) 33 weeks (27-38) versus 37 (29-41), P < 0.005 pre-eclampsia and 35 weeks (25-41) versus 38 (25-42), P < 0.001 normotensive]. In pre-eclampsia the concomitant occurrence of SGA second twin and the discordance >25% was associated with shorter gestation while the presence of SGA second twin alone was not.     

The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs. Trial Registry Name: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, small-for-gestational-age babies and spontaneous preterm birth (https://www.anzctr.org.au). Registration number: ACTRN12607000551493.     

The use of metformin for women with PCOS undergoing IVF treatment

BACKGROUND: Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). We wished to explore the effect of metformin in women with PCOS undergoing IVF. METHODS: A randomized, placebo-controlled, double-blind study was carried out between 2001 and 2004. Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were randomized to receive metformin (MET), 850 mg, or placebo (PLA) tablets twice daily from the start of the down-regulation process until the day of oocyte collection. The primary outcome was to be an improvement in the overall fertilization rate. RESULTS: One-hundred and one IVF/ICSI cycles were randomized to receive metformin (52) or to receive placebo (49). There was no difference in the total dose of rFSH required per cycle (median dose: MET = 1200 U, PLA = 1300 U; P = 0.937). The median number of oocytes retrieved per cycle (MET = 17.2, PLA = 16.2; P = 0.459) and the overall fertilization rates (MET = 52.9%, PLA = 54.9%; P = 0.641) did not differ. However, both the clinical pregnancy rates beyond 12 weeks gestation per cycle (MET = 38.5%, PLA = 16.3%; P = 0.023) and per embryo transfer (MET = 44.4%, PLA = 19.1%; P = 0.022) were significantly higher in those treated with metformin. Furthermore, a significant decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) was observed (MET = 3.8%, PLA = 20.4%; P = 0.023), and this was still significant after adjustment for BMI, total rFSH dose and age (OR = 0.15; 95% CI: 0.03, 0.76; P = 0.022). CONCLUSION: Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.     

A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome

This meta-analysis was conducted to compare outcomes of conventional IVF in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. Studies in which PCOS patients undergoing IVF were compared with a matched--no male factor--control group were considered for this review. A definition consistent with the Rotterdam consensus criteria of PCOS was required, and all patients within a given study had to be treated with the same ovarian stimulation protocol. Information regarding patient characteristics and pregnancy outcome was also required. Nine out of 290 identified studies reporting data on 458 PCOS patients (793 cycles) and 694 matched controls (1116 cycles) fulfilled these inclusion criteria. PCOS patients demonstrated a significantly reduced chance of oocyte retrieval per started cycle, odds ratio (OR) = 0.5 [95% confidence interval (CI) = 0.2-1.0]. However, no difference was observed in chance of embryo transfer per oocyte retrieval between the groups (OR = 0.7, 95% CI = 0.4-1.3). Significantly more oocytes per retrieval were obtained in PCOS patients compared with controls [random effects estimate 3.4 [95% (CI) = 1.7-5.1)]. The number of oocytes fertilized did not differ significantly between PCOS patients and controls, weighted mean difference (WMD) 0.1 oocytes (95% CI = 21.4-1.6). No significant difference was observed in the clinical pregnancy rates per started cycle, OR = 1.0 (95% CI = 0.8-1.3). The incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported. This meta-analysis demonstrates an increased cancellation rate, but more oocytes retrieved per retrieval and a lower fertilization rate in PCOS undergoing IVF. Overall, PCOS and control patients achieved similar pregnancy and live birth rates per cycle.