Biochemical markers of placental dysfunction in assisted conception

A possible mechanism for poor perinatal outcomes in singleton pregnancies conceived following assisted reproductive technologies (ART) and those conceived naturally following a period of infertility (>12 months) is thought to be placental dysfunction. This was investigated by measuring plasma concentrations of biochemical markers: (i) soluble fms-like tyrosine kinase1 (sFlt1); (ii) placental growth factor (PlGF); (iii) leptin; and (iv) plasminogen activator inhibitor 2 (PAI-2), serially at four antenatal time points. Baseline concentrations of each marker after delivery were also measured. The control group was naturally conceived singleton pregnancies with no history of infertility. Non-smoking, age-matched nulliparous women with no significant medical history were recruited to all groups. The ART group had significantly lower mean plasma concentrations of PlGF at all antenatal time points compared to the control group (p?p?相似文献   

Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age

Objectives. Preeclampsia is considered an anti-angiogenic state. A role for the anti-angiogenic factors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin in preeclampsia has been proposed. Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) has been detected in human plasma, and the recombinant form of this protein has anti-angiogenic activity. There is a paucity of information about maternal plasma sVEGFR-2 concentrations in patients with preeclampsia and those without preeclampsia with small for gestational age (SGA) fetuses. This study was conducted to determine whether: (1) plasma sVEGFR-2 concentration changes throughout pregnancy; and (2) preeclampsia and SGA are associated with abnormalities in the maternal plasma concentration of sVEGFR-2.

Study design. This cross-sectional study included non-pregnant women (n = 40), women with normal pregnancies (n = 135), women with an SGA fetus (n = 53), and women with preeclampsia (n = 112). SGA was defined as an ultrasound-estimated fetal weight below the 10^th percentile for gestational age that was confirmed by neonatal birth weight. Plasma concentrations of sVEGFR-2 were determined by ELISA.

Results. (1) There was no significant difference in the mean plasma concentration of sVEGFR-2 between non-pregnant women and those with normal pregnancies (p = 0.8); (2) patients with preeclampsia and those without preeclampsia with SGA fetuses had a lower mean plasma concentration of sVEGFR-2 than that of women with normal pregnancies (p < 0.001 for both); and (3) there was no significant difference in the mean plasma concentration of sVEGFR-2 between patients with preeclampsia and those without preeclampsia with SGA (p = 0.9).

Conclusions. Preeclampsia and SGA are associated with low plasma concentrations of sVEGFR-2. One interpretation of the findings is that plasma sVEGFR-2 concentration could reflect endothelial cell function.     

A pilot study to determine whether progestogen supplementation using dydrogesterone during the first trimester will reduce the incidence of gestational hypertension in primigravidae

Background: Gestational hypertension (GH) remains one of the main causes of high maternal and perinatal morbidity and mortality worldwide with the highest incidence among primigravidae of about 10%–15%. However, it was noted that the incidence of GH in primigravidae who conceived following assisted reproductive technique (ART) or intrauterine insemination (IUI) supplemented with dydrogesterone during the first trimester was low.

Aim: To determine whether dydrogesterone supplementation during the first trimester can reduce the incidence of GH among primigravidae.

Method: A prospective cross-sectional comparative study was undertaken in 2010 on 116 primigravidae (study group) who conceived following ART or IUI and supplemented with dydrogesterone up to 16 weeks gestation. They were matched for age and race at 16 weeks gestation with a control patient from the early pregnancy clinic who were primigravidae (n?=?116) who conceived spontaneously without dydrogesterone supplementation.

Findings: The incidence of GH in the study group was significantly lower than the control group (1.7% versus 12.9%, p?=?0.001). The incidence of fetal distress was also significantly lower in the study group compared to the control group (4.3% versus 18.1%, p?=?0.001).

Interpretation: Dydrogesterone supplementation during the first trimester significantly reduced the incidence of GH and fetal distress in primigravidae.     

Ectopic pregnancy risk with assisted reproductive technology procedures

OBJECTIVE: To assess the ectopic pregnancy risk among women who conceived with assisted reproductive technology (ART) procedures. METHODS: The ectopic rate for ART pregnancies was calculated from population-based data of pregnancies conceived with ART in U.S. clinics in 1999-2001. Variation in ectopic risk by patient and ART treatment factors was assessed by using bivariate analyses and multivariable logistic regression. RESULTS: Of 94,118 ART pregnancies, 2,009 (2.1%) were ectopic. Variation was observed by procedure type. In comparison with the ectopic rate (2.2%) among pregnancies conceived with in vitro fertilization and transcervical transfer of freshly fertilized embryos from the patient's oocytes (fresh, nondonor IVF-ET), the ectopic rate was significantly increased when zygote intrafallopian transfer (ZIFT) was used (3.6%) and significantly decreased when donor oocytes were used (1.4%) or when a gestational surrogate carried the pregnancy (0.9%). Among fresh nondonor IVF-ET procedures, the risk for ectopic pregnancy was increased among women with tubal factor infertility (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.7-2.4; referent group = ART for male factor), endometriosis (OR 1.3, 95% CI 1.0-1.6), and other nontubal female factors of infertility (OR 1.4, 95% CI 1.2-1.6) and decreased among women with a previous live birth (OR 0.6, 95% CI 0.5-0.7). Transfer of embryos with an indication of high implantation potential was associated with a decreased ectopic risk when 2 or fewer embryos were transferred (OR 0.7, 95% CI 0.5-0.9), but not when 3 or more embryos were transferred. CONCLUSION: Ectopic risk among ART pregnancies varied according to ART procedure type, reproductive health characteristics of the woman carrying the pregnancy, and estimated embryo implantation potential. LEVEL OF EVIDENCE: II-2.     

Maternal Mental Health in Assisted and Natural Conception: A Prospective Cohort Study

ObjectiveThis study sought to compare the pregnancy and postpartum self-reported mood and mental health status of women who conceived with assisted reproductive technology (ART) with those of women who conceived spontaneously.MethodsIn this prospective cohort study, 1176 pregnant women from prenatal clinics in the Ontario Birth Study were enrolled. In the pregnancy and the postpartum period, women who conceived with ART, including in vitro fertilization and intrauterine insemination, were compared with women who conceived spontaneously regarding depression and anxiety at 12–16 weeks and 24–28 weeks gestation and 6–10 weeks postpartum. The following main outcome measures were used: Edinburgh Postnatal Depression Scale, two-item Patient Health Questionnaire, State Trait Anxiety Inventory six-item scale, and two-item Generalized Anxiety Disorder scale (Canadian Task Force Classification II-2).ResultsWomen who conceived with ART demonstrated a decreased likelihood of depression compared with women who spontaneously conceived (SC) at 24–28 weeks gestation (Edinburgh Postnatal Depression Scale: ART 3.6% vs. SC 15%; P < 0.01; two-item Patient Health Questionnaire: ART 0.0% vs. SC 4.0%; P = 0.027), as well as decreased perceived stress (mean score: ART 3.25 vs. SC 4.02; P < 0.01). Women in the ART group also had a lower percentage of positive two-item Generalized Anxiety Disorder scores (ART 2.7% vs. SC 7.5%; P = 0.049). There was no difference in self-reported depression, anxiety, or perceived stress between groups at 12–16 weeks gestation or at 6–10 weeks postpartum.ConclusionWomen who conceived using ART reported decreased rates of depressive symptoms, perceived stress, and generalized anxiety during the second trimester of pregnancy compared with women who had SC pregnancies, and both groups experienced similar mental health status earlier in gestation and in the postpartum period.     

Pre-birth characteristics and 5-year follow-up of women with cryopreserved embryos after successful in vitro fertilisation treatment

Many patients do not make a decision about the disposition of their surplus embryos until they are compelled to do so by statutory limits. In the current study, the characteristics of women who had conceived through in?vitro fertilisation (IVF) and who still had embryos stored (E-S; n?=?26) 5 years after IVF were compared to a cohort comparison group (C-C; n?=?40). At time 1 (T1, 28 weeks pregnant) women completed questionnaires on personality traits (anxiety, locus of control and dependency) and participated in an interview on socio-demographic characteristics, family composition and stored embryos. At T2 (5 years later) women were re-interviewed and asked about beliefs about the embryos. Women in the E-S group were significantly younger, had been married or living with their partner for fewer years and had had more children than the C-C group. Further, women in the E-S group were more likely to have an external locus of control and a dependent personality than women in the C-C group. Almost all women in the E-S group (88.5%) thought of their embryos as siblings to existing children, and reported thinking about the embryos occasionally (61.5%) or frequently (34.6%). The personality differences identified may suggest that women who still have embryos after the end of fertility treatment may be in need of decision support.     

Unexplained fetal death is associated with increased concentrations of anti-angiogenic factors in amniotic fluid

Objective.?Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors.

Study design.?This cross-sectional study included patients with fetal death (n?=?35) and controls (n?=?129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained (n?=?25); (2) preeclampsia and/or placental abruption (n?=?5); and (3) chromosomal/congenital anomalies (n?=?5). The control group consisted of patients with preterm labor (PTL) who delivered at term (n?=?92) and women at term not in labor (n?=?37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied.

Results.?(1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group (p?<?0.001 for each); (2) these results remained significant among different subgroups of stillbirth (p?<?0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR?=?10.8; 95%CI 1.3–89.2 and adjusted OR 87; 95% CI 2.3–3323, respectively).

Conclusion.?Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations.     

Multifetal gestations with assisted reproductive technique before the single-embryo transfer legislation: obstetric,neonatal outcomes and congenital anomalies

Objective: To compare perinatal, neonatal outcome and congenital anomalies of multiple gestations conceived by means of assisted reproductive techniques with spontaneously conceived multiples before the limitation of number of embryo transfer.

Methods: Cases consisted of assisted reproductive technique (ART) multifetal gestations and control group comprised of spontaneously conceived multifetal gestations delivered in the same time period. Outcomes were perinatal, neonatal outcome, long-term outcomes and congenital anomalies of multiple gestations. There were 270 multifetal pregnancies for analysis, of which 137 were achieved by ART and 133 were spontaneous in this prospective study.

Results: Incidences of preeclampsia, gestational diabetes, deep vein thrombosis, thrombocytopenia, intrahepatic cholestasis and preterm premature rupture of membranes were similar in ART and spontaneous groups. There was no difference in fetal malformation rates between ART and control group, but higher rates of central nervous system malformation were observed (4 (1.5%) in control, 0 in ART group, p?=?0.04) in spontaneous group. No difference was seen in the perinatal mortality.

Conclusions: Neonatal and maternal outcomes are comparable between ART and spontaneous multifetal gestations. Congenital fetal malformation rates between ART and spontaneous multifetal pregnancies were similar except central nervous system malformation that was more likely in spontaneously conceived ones.     

An imbalance between angiogenic and anti-angiogenic factors precedes fetal death in a subset of patients: results of a longitudinal study

Objective.?Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF).

Methods.?This retrospective longitudinal nested case–control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n?=?124); and (2) patients who had a fetal death (n?=?19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis.

Results.?(1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates (p?<?0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation (p?<?0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation (p?=?0.04) and became higher than those of controls between 20 and 40 weeks of gestation (p?<?0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation (p?<?0.05); (5) The ratio of PlGF/(sVEGFR-1?×?sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94–781%) and significantly lower (44–75%) than those in normal pregnant women between 20 and 40 weeks of gestation (p?<?0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation.

Conclusions.?Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters.     

The effect of anti-thyroid antibodies on endometrial volume,embryo grade and IVF outcome

Thyroid auto-immunity (TAI) has been implicated as the most common cause of hypothyroidism in general population, especially in women. Many studies revealed that increased infertility incidences with TAI. The aim of the present article was to evaluate the effect of thyroid auto-antibody (TAA) positivity on embryological parameters, IVF-outcome and endometrial volume (EnV) in infertile patients who were applied for routine artificial reproductive technologies (ART) programme. This study included prospective, sequential, cross-sectional analyses of parameters obtained from 69 patients with unexplained infertility. It was the first ART application of patients. Patients were homogenous for age, body mass index, basal hormone measurements and underwent same ovulation induction protocol. They were evaluated for thyroid hormone profile and TAAs and divided into three groups; TAA negative group (n = 31), TAA positive group (n = 23) and TAA positive and euthyroid with medication group (n = 15). There were no differences among groups for the number of Grade-1 and Grade-2 embryos, distribution of embryo-grades, number of oocytes retrieved and fertilised, biochemical pregnancy ratios (PR), EnV and miscarriage ratio. However, the clinical PR was significantly lower in the TAA positive group (p = 0.024). In conclusion, the embryo grades and EnV did not differ among groups. But the clinical PR differs and the anti-thyroid peroxides positivity, above the cut-off point, affects the clinical PR.     

A comparison of quality of life following spontaneous conception and assisted reproduction

ObjectiveTo compare the levels of and changes in quality of life (QoL) during pregnancy between couples who conceived spontaneously and couples who underwent successful treatment by assisted reproductive technology (ART).MethodsIn a survey at the Santa Maria Nuova Hospital, Reggio Emilia, Italy, between September 11, 2009, and May 25, 2011, 230 individuals (57 ART couples and 58 couples who conceived spontaneously) completed Short-Form 36 on QoL at 22 and 32 gestational weeks.ResultsCompared with men, women had lower scores in most dimensions of QoL regardless of the method of conception; women also showed a decrease in physical and social QoL during pregnancy that was not evident among men. Compared with non-ART couples, ART couples had lower physical (especially women) and social QoL; ART couples also showed a decrease in social QoL from the second to the third trimester that was not observed among non-ART couples.ConclusionThe results underline the higher burden that pregnancy represents for women on a physical and social level. ART treatment seems to increase the negative impact of pregnancy on QoL in the couple as a whole; early support in adjusting to the realities and demands of pregnancy might prove beneficial for these future parents.     

Linking back-to-back stimulation cycles with oral contraceptives or progestins in women undergoing embryo accumulation for preimplantation genetic testing,a retrospective study

Abstract

The purpose of this study was to determine the pregnancy rate in the double sequential transfer of embryos on both day 3 and day 5 compared to day 5 alone, in in vitro fertilization-embryo transfer (IVF/ET) in patients with the three repeated consecutive IVF failures. In this controlled trial, women scheduled for IVF/ET with the three repeated consecutive IVF failures were randomized to either sequential transfer of embryos on day 2 and on day 5 after ovum pick-up (group 1, n = 60) or blastocyst ET on day 5 (group 2, n = 60) as a control group. The primary outcome measures were the chemical and clinical pregnancy rate. Baseline and cycle characteristics were comparable in both groups. Chemical and clinical pregnancy rate was similar in the sequential ET group (40%) compared to the day 5 of ET group (38.3%) (p value = .85). It seems that the double ET does not increase the chance of pregnancy rate compared to blastocyst ET on day 5 in the patients with the three repeated IVF-ET failures.     

Anger in women treated with assisted reproductive technology (ART): effects on mother and newborn

Objective: To assess anger, as well as other negative emotions, in women who underwent assisted reproductive technology (ART) respect to women who conceived naturally, and explore the effect of anger on neonatal outcomes.

Methods: We recorded personal and obstetric history of the patients, neonatal weight, Apgar score, obstetric and neonatal complications. We performed Structural Clinical Interview for DSM-SCID I and II in order to assess the DSM IV axis I and axis II, State-Trait Anger Expression Inventory 2 (STAXI-2), the Self-rating Depression Scale (SDS) and Self-rating Anxiety scale (SAS).

Results: On the STAXI-2 scale, the ART group scored higher than the natural conception group on measures of general tendency and personality disposition to get angry. Moreover, the ART group women showed quite low levels of tolerance to negative environmental feedback. Our results further suggest that trait anger provides the most meaningful contribution as predictor of weight at birth. No significant differences were found for anxiety and depression between the two groups.

Conclusions: Our study highlights the important role of anger during pregnancy, and suggests the need for further studies on both biochemical and behavioural patterns in larger samples of women who became pregnant by ART.     

Premature expression of the decidualization marker prolactin is associated with repeated implantation failure

Abstract

Repeated implantation failure (RIF) is a poorly understood reproductive pathology defined by the inability to achieve a clinical pregnancy in at least three consecutive IVF cycles. In this study, we investigated whether the onset of decidualization, marked by prolactin (PRL) expression, is associated with RIF. We performed a retrospective cohort study using endometrial biopsies from women with idiopathic subfertility, that conceived naturally during the same cycle in which the biopsy was taken (group 1; n?=?15) conceived naturally within three months after the biopsy was taken (group 2; n?=?20), or unsuccessfully underwent six IUI cycles and three IVF cycles with transfer of at least one high-quality embryo (group 3, RIF; n?=?20). Our results demonstrated that immunohistochemical PRL-staining was present in 8/15 women from group 1 (53.3%), in 1/20 women from group 2 (5.0%), and in 11/20 women from group 3 (55.0%). Increased proliferation, analyzed by Ki67 expression, was seen in women that were pregnant during the biopsy, compared to all women combined that were not pregnant (p≤.01). In conclusion, our study demonstrates that premature expression of the decidualization marker PRL during the luteal phase is associated with RIF.     

Foetal thymus size in pregnancies after assisted reproductive technologies

Purpose

The aim of our study was to compare thymus sizes in foetuses conceived using assisted reproductive technologies (ART) to those conceived naturally (control group).

Methods

Sonographic foetal thymus size was assessed retrospectively in 162 pregnancies conceived using ART and in 774 pregnancies conceived naturally. The anteroposterior thymic and the intrathoracic mediastinal diameter were measured to calculate the thymic–thoracic ratio (TT-ratio). The ART cases were subdivided into two groups: (1) intracytoplasmic sperm injection (ICSI; n?=?109) and (2) in vitro fertilisation (IVF; n?=?53).

Results

The TT-ratio was smaller in pregnancies conceived using ART (p?<?0.001). In both ART subgroups (ICSI and IVF), the TT-ratio was lower compared to the control group (p?<?0.001). However, no difference between the two subgroups could be detected (p?=?0.203).

Conclusions

Our data show reduced thymus size in foetuses conceived using ART compared to controls. These findings indicate that the use of ART may lead to certain deviations in organogenesis.

     

Obesity and ultrasound-estimated visceral fat deposits in women undergoing Assisted Reproductive Technology (ART) procedures

The aim of this study was to evaluate the influence of body mass index (BMI) and ultrasound-estimated visceral adipose tissue deposits on oocyte quality and pregnancy rate in women undergoing Assisted Reproductive Technology (ART) procedures. The study included 58 women who underwent ART procedures. According to their BMI, the women were divided into normal weight and overweight/obese; an ultrasound evaluation of preperitoneal fat thickness (PFT) was also performed for each patient. The oocyte quality was then assessed, and samples of follicular fluid were collected from each woman, in order to evaluate the intrafollicular concentration of reactive oxygen species (ROS) as markers of oxidative stress and pro-inflammatory cytokines (IL-1β and IL-6) as markers of chronic inflammation. A negative correlation was found between BMI (as well as PFT) and the number of retrieved oocytes (r?=??0.3; p?<0.05 and r?=??0.5; p?r?=??0.4; p?=?<0.05) and obtained embryos (r?=??0.3; p?相似文献   

Effects of assisted reproductive technology and of women’s quality of life on depressive symptoms in the early postpartum period: a prospective case-control study

Abstract

This study explored the influence of both assisted reproductive technology (ART) and reduced quality of life (QoL) during pregnancy on postpartum blues (PPB). Sixty-three sub-fertile patients who conceived through ART and 72 women who naturally conceived were enrolled in this prospective study. At 22nd and 32nd gestational weeks, women completed the Edinburgh Postnatal Depression Scale (EPDS) and the Short-Form 36 (SF-36), to investigate depressive symptoms and QoL, respectively; EPDS was again used at 15 days after birth to assess PPB. At both time points, higher EPDS scores and lower mental well-being scores (SF-36) significantly predicted PPB. The number of previous ART cycles emerged as the strongest predictor, whereas no significant effect was observed for the conceiving method. The results suggest the usefulness of assessing QoL during pregnancy and considering previous ART failures in preventing PPB.     

Impact of quantitative parameters,such as number of retrieved oocytes,number of transferred embryos and availability of surplus embryos for cryopreservation,on clinical pregnancy rates in ART

Abstract

Objective: To estimate the impact of quantitative parameters such as number of retrieved oocytes, number of transferred embryos and availability of surplus embryos for cryopreservation on clinical pregnancies in assisted reproductive technology (ART).

Design: We used the database of fertility clinic on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment cycles from year 2000 to 2010. Follicular fluids containing oocyte–cumulus complexes were recovered by a single lumen follicle aspiration needle, and IVF or ICSI procedure was used depending on infertility indications. Fertilization determination was performed on the second day. Zygotes were transferred into fresh medium and cultivated until the embryo transfer procedure. According to morphological criteria, the best quality embryos were transferred into uterus on the second or third day. Surplus embryos were frozen by slow freezing or by vitrification. We evaluated only clinical pregnancies that were diagnosed by ultrasonography.

Patients: We allocated all 1161 women cohort into three age groups: 671 women were <35; 397 were 35–40 years old and 93 women were >40. Indications for IVF treatment were as follows: mechanical factor (436 cases), male infertility (361 cases), idiopathic infertility (129 cases), endometriosis (78 cases), immunological infertility (14 cases), anovulation (28 cases), and other indications (28 cases). There were no data about the cause of infertility of 87 patients. The stimulation protocol was composed from gonadotropin hormone stimulation with antagonist or agonist supplementation. The triggering of luteinizing hormone (LH) surge was performed by recombinant human chorionic gonadotropin (hCG). The clinical pregnancy rates were: 42.2% (283/671) for women <35, 31.2% (124/397) for women 35–40-year-old and 16.1% (15/93) for women >40.

Interventions: All materials and methods that we used were based on results from our daily practice in IVF clinic and have no experimental design.

Main outcome measures: We evaluated clinical pregnancies in terms of the number of obtained oocytes, the amount of transferred embryos and the availability of surplus embryos for freezing. The number of retrieved oocytes was divided as follows: 1–5 (group I); 6–10 (group II); ≥11 (group III). The number of transferred embryos was from 1 to 3. Cases at which cryopreservation of embryos was not performed were evaluated as well.

Results: For women <35 and 35–40 years old, the highest percentage of pregnancies was achieved when 11 and more oocytes were obtained. Differences in women under 35 between groups were statistically significant. Statistically significant differences in clinical pregnancies depend on the number of transferred embryos in the age groups of <35 and 35–40. Women <35 and 35–40 years old, with the availability of surplus embryos for freezing, had better chances for pregnancy compared with women, who had no excess embryos for freezing.

Conclusions: The number of obtained oocytes, the number of transferred embryos and the availability of surplus embryos for freezing may serve as predictors of pregnancy rates in ART.     

Outcome of IVF in DES-Exposed Daughters: Experience in the 90s

Purpose: The outcome of in vitro fertilization (IVF) in a group of infertile women with a history of in utero exposure to diethylstilbestrol (DES) was analyzed. Records from an academic IVF program were retrospectively reviewed. Methods: Seventeen infertile women with a self-reported history of exposure to DES in utero, attending the IVF unit at Massachusetts General Hospital (MGH) for assisted reproductive technology (ART), underwent 27 IVF cycles. Analysis of the outcome of IVF including implantation and ongoing pregnancy rates was performed. The data were compared with results from a group of 20 infertile patients with idiopathic infertility undergoing 27 IVF cycles at MGH during the same period. The patients in the two groups were matched for age, basal day 3 levels of follicle stimulating hormone and serum estradiol, and the number and quality of embryos transferred. Results: The response to controlled ovarian hyperstimulation was comparable in the two groups. Significantly lower implantation and ongoing pregnancy rates following IVF and embryo transfer were seen in the utero DES-exposed group compared to the control patients. Conclusions: Infertile patients with a history of in utero exposure to DES exhibit a significantly impaired implantation rate following IVF, and the outcome of ART remains poor.     

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Abstract

Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis.

Methods: This cross-sectional study included women with preeclampsia (n?=?106) and women with an uncomplicated pregnancy (n?=?131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte.

Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p?<?0.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p?=?0.7 and p?=?1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman’s Rho?=?0.72 and 0.63; each p?<?0.0001), and negatively with PlGF (Spearman’s Rho?=??0.56, p?<?0.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (<37 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors.

Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the utero-placental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic factors. It remains to be elucidated if an elevation of maternal plasma sST2 concentrations in pregnancy is specific to preeclampsia.