Early pregnancy loss in in vitro fertilization (IVF) is a positive predictor of subsequent IVF success

OBJECTIVE: To determine the significance of biochemical pregnancy losses and clinical spontaneous abortion (SAB) on outcomes of future IVF cycles. DESIGN: Retrospective cohort study. SETTING: Academic IVF program. PATIENT(S): Women with a history of unsuccessful IVF attempts undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Patients with an early pregnancy loss had a greater ongoing clinical pregnancy rate in the immediate next cycle when compared with those women who had a negative pregnancy test (37.3% vs. 27.3%). Patients with a history of a biochemical pregnancy or a clinical spontaneous abortion had an ongoing clinical pregnancy rate in the next cycle of 38.4% and 42.3%, respectively, compared with 27.3% in women who had a history of a negative pregnancy test. The cumulative pregnancy rate after the first IVF attempt was 54.1% in patients with a previous biochemical pregnancy loss, 61.4% in those with a previous clinical SAB, and 46.5% in women with a previous negative pregnancy test. CONCLUSION(S): Women who experience an early pregnancy loss after IVF have a greater likelihood of success in subsequent IVF cycles when compared with patients who fail to conceive.     

Acute and chronic presentation of ectopic pregnancy may be two clinical entities

OBJECTIVE: The diagnosis of ectopic pregnancy (EP) is often confirmed at presentation (acute), but often requires serial beta-hCG levels to confirm the diagnosis (chronic). The purpose of this study is to analyze whether these clinical presentations represent a spectrum of disease. DESIGN: The retrospective cohort study of 452 patients diagnosed with EP at the University of Pennsylvania in the years 1990-1999. SETTING: University of Pennsylvania, Philadelphia, Pennsylvania. PATIENT(S): Four hundred fifty-two patients diagnosed with EP. Patients diagnosed with EP were divided into two groups according to the time of diagnosis. MAIN OUTCOME MEASURE(S): A total of 37 parameters were examined including historic and demographic factors, findings at presentation, and treatment and outcome variables. RESULT(S): The two groups were similar in terms of historic EP risk factors. Multivariable analysis demonstrates that women with a chronic presentation were less likely to have received fertility medications (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06-0.84), less likely to present with pain (OR 0.29; 95% CI 0.12-0.71), have a lower beta-hCG level at presentation (9,849 mIU/mL +/- 16,726 vs. 1,787 mIU/mL +/- 4,717), lower chance of rupture (OR 0.19; 95% CI 0.05-0.73), and less frequently have blood type 0. CONCLUSION(S): Women diagnosed with ectopic pregnancy can be categorized into two groups, those with an acute presentation and those with a chronic presentation. Differences in risk factors, presentation, and outcome may reflect differences in trophoblast viability or invasive potential.     

Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker?

Objective: To determine serum levels of vascular endothelial growth factor (VEGF) and evaluate their capacity to serve as a marker for the diagnosis of ectopic pregnancy (EP).

Design: Prospective, case-controlled study.

Setting: A tertiary care center.

Patient(s): Twenty women with EP, 10 women with normal intrauterine pregnancy, and 10 women with abnormal intrauterine pregnancy, all at comparable stages of gestation.

Intervention(s): Serum samples were obtained from all women.

Main Outcome Measure(s): All samples were analyzed for VEGF, progesterone, and β-hCG by specific methods.

Result(s): Women with EP had higher serum levels of VEGF than women with normal intrauterine pregnancy and women with abnormal intrauterine pregnancy (median levels, 226.8 pg/mL, 24.4 pg/mL, and 59.4 pg/mL, respectively). With a cutoff level of 200 pg/mL, serum VEGF could distinguish intrauterine from extrauterine pregnancy with a sensitivity of 60%, specificity of 90%, and positive predictive value of 86%.

Conclusion(s): The increased serum VEGF levels in women with EP may facilitate this challenging diagnosis and reduce maternal morbidity and mortality.     

行IVF/ICSI各年龄段妇女早期单、双胎妊娠丢失的回顾性研究

目的:分析行IVF/ICSI的各年龄段妊娠妇女早期单、双胎妊娠胚胎丢失的影响因素。方法:回顾性分析行IVF/ICSI治疗,授精后第2日或第3日移植2~3个胚胎后单、双胎妊娠周期中早期妊娠囊丢失情况。结果:共收集到1 674个IVF/ICSI周期,孕6周单胚胎着床1 077例,双胚胎着床597例。孕12周时单胎和双胎的继续妊娠数分别为901例(83.66%)和548例(91.79%)(P<0.001)。双胎妊娠中,21例(3.52%)自然减胎成单胎,28例(4.69%)自然流产。单胎和双胎妊娠中,每个着床妊娠囊的丢失率分别为16.34%(176/1 077),6.45%(741/1 194)(P<0.001)。妊娠妇女早期妊娠囊丢失率单胎者高于同年龄段双胎妊娠者,26~37岁各年龄段妇女单胎与双胎妊娠丢失率间差异均有统计学意义(P<0.05),≥38岁妇女双胎妊娠丢失率显著增加。单胎妊娠组Gn每日用量显著高于双胎妊娠组(P<0.05),而受精率及优质胚胎率单胎妊娠组显著低于双胎妊娠组(P<0.001),Gn每日用量、受精率及优质胚胎率在妊娠丢失组和继续妊娠组间无统计学差异(P>0.05)。结论:双胎妊娠早期能获得更好的继续妊娠机会,随年龄增加尤其是≥38岁妇女,妊娠丢失显著上升。胚胎形态学质量好则有助于双胚胎着床,但是对继续妊娠没有直接明显的影响。     

Does hydrosalpinx reduce the pregnancy rate after in vitro fertilization?

Objective: To determine the effect of hydrosalpinges on the pregnancy rate in an IVF program.

Design: Multicentric retrospective analysis of clinical and laboratory data.

Setting: Two assisted reproductive technology centers in university hospitals.

Patient(s): Four hundred forty-three women, under 38 years of age, with pure tubal infertility. The patients were classified into the following five groups: bilateral hydrosalpinges (n = 37), unilateral hydrosalpinx (n = 54), bilateral tubal occlusion (n = 207), unilateral tubal occlusion (n = 55), and severe tubal disease without complete occlusion (n = 90).

Main Outcome Measure(s): Pregnancy and implantation rates.

Result(s): The pregnancy and the implantation rates per transfer (12.3% and 5.4%) obtained by women with bilateral hydrosalpinges are significantly lower than the rates (means = 23.1% and 12%) for all other tubal infertility groups.

Conclusion(s): Bilateral hydrosalpinges have a deleterious effect on the outcome of IVF program.     

Increased body mass index has a deleterious effect on in vitro fertilization outcome

Purpose: Few studies have addressed the effect of weight on IVF outcome, with some showing a decrease in IVF success and some showing no change in overweight women (BMI > 25 kg/m²) compared to women with normal weight (BMI < 25 kg/m²). Methods: One hundred thirty-nine women <40 years old undergoing 180 IVF cycles with fresh embryo transfers were retrospectively evaluated between January 1997 and March 1999, stratified by body mass index (BMI) (cutoff of 25). Results: In the group with BMI > 25 kg/m², basal FSH, implantation rates (IR), and pregnancy rates (PR) were significantly lower, while the duration of stimulation, gonadotropin requirements, and spontaneous miscarriages were slightly higher, compared to the BMI 25 group. Conclusions: Excess weight defined as BMI > 25 kg/m² has a negative impact on IVF outcome. Future prospective studies evaluating oocyte and/or embryo quality, and androgen and insulin levels, between overweight women and those with normal weight are needed.     

Transmyometrial oocyte retrieval and pregnancy rates

OBJECTIVE: To determine whether transvaginal, ultrasound-guided oocyte retrieval performed through the myometrium has a negative impact on IVF pregnancy rates. DESIGN: Retrospective cohort study. SETTING: Academic hospital and research center. PATIENT(S): A total of 5,115 IVF cycles performed at the Brigham and Women's Hospital between 1998 and 2001 were evaluated. In 85 cycles (1.7%), the oocyte retrieval needle passed through the myometrium because of ovarian position during retrieval. Each of these cases was matched to a control cycle by age, attempt number, and date of retrieval. INTERVENTION(S): Transmyometrial oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): There were no statistically significant differences in pregnancy rates between cases and controls. Cases were more likely than controls to have underlying tubal disease and adhesions as the primary cause of infertility. The groups did not differ significantly in terms of age, attempt number, estradiol level, follicle number, days stimulated, ampules of gonadotropins administered, number of eggs, number of embryos, or quality of embryos. CONCLUSION(S): Transmyometrial oocyte retrieval is an uncommon event. Clinicians and patients can be reassured that transmyometrial oocyte retrieval does not seem to decrease IVF pregnancy rates; however, a larger study with greater power might reveal a statistically significant difference.     

Screening for Down syndrome in dichorionic twin pregnancies conceived by in vitro fertilization (IVF): a clinical pilot study to confirm the laboratory methods

Purpose

The corrections necessary to estimate the risk for Down syndrome in twin pregnancies have been pointed out. We performed a nested controlled study to evaluate the validity of these corrections in dichorionic twins conceived by IVF.

Methods

Detailed clinical data was collected from the medical records. Twins were matched with a contemporaneous cohort of spontaneously conceived singleton pregnancies that serve as reference in a 1 to 4 ratio. All patients had their entire obstetrical care at our Hospital. The Student t-test was used for group comparisons and a p-value <0.05 was considered significant.

Results

Nineteen sets of normal twins concordant in size and with appropriate weight for gestational age were matched with 80 normal and mature newborns. Significant differences between groups were found for maternal age, gestational age at delivery and newborn weight (all p < 0.01). No statistical differences were noted for the levels of the biochemical markers expressed as multiples of the median. However, a 15 % closer approximation to the laboratory median for PAPP-A and a 10 % closer approximation to the laboratory median for free β-hCG was evident in twins when compared to the reference group.

Conclusions

These findings support the methods used to estimate the risk for Down syndrome in dichorionic twin pregnancies conceived after IVF. A future study with a larger sample size could confirm if the laboratory corrections done on the combined screening test improve the predictability of Down syndrome in dichorionic twin pregnancy conceived by IVF when compared to singleton pregnancies.     

Transvaginal ultrasound-guided embryo transfer improves outcome in patients with previous failed in vitro fertilization cycles

OBJECTIVE: To determine the effect of transvaginal ultrasound-guided ET in IVF cycles performed on patients who had previously failed to conceive from IVF and compare the results to previous cycles where ultrasound guidance was not used. DESIGN: Retrospective clinical study.Setting: Private practice IVF program. PATIENT(S): One hundred twenty-nine women undergoing consecutive cycles of IVF where fresh embryos were transferred. INTERVENTION(S): Transvaginal ultrasound guidance was used during transfer of embryos. MAIN OUTCOME MEASURE(s): Patient age, number of ampules of gonadotropin used, maximum E(2) level, number of oocytes retrieved, number of two pronuclei embryos obtained, number of embryos transferred, mean embryo score, implantation and pregnancy rate. RESULT(S): There was no difference in any of the clinical parameters measured in IVF cycles resulting in pregnancy when transvaginal ultrasound-guided ET was used compared to the failed cycles when there was no ultrasound guidance. Of the patients who previously had failed IVF cycles and subsequently had IVF cycles with ultrasound guidance, those who became pregnant had higher mean embryo scores than those who did not become pregnant. Overall implantation and pregnancy rates were higher during the study period when transvaginal ultrasound guidance was used than in the previous 3 years when it was not used. CONCLUSION(S): Transvaginal ultrasound-guided ET may be responsible for successful IVF cycles in patients who had previously failed to conceive when embryos were transferred by the clinical touch method. Transvaginal ultrasound guidance may also be responsible for an overall increase in embryo implantation and pregnancy compared to the use of the clinical touch method.     

体外受精-胚胎移植技术中74例异位妊娠的临床分析

目的:分析体外受精-胚胎移植(in vitro fertilization and embryo tranfer,IVF-ET)助孕技术中发生异位妊娠的影响因素、诊断、治疗方法及预防措施。方法:回顾性分析IVF-ET助孕技术中发生异位妊娠74例患者的临床资料。结果:所有接受IVF-ET的1 585患者中,共发生异位妊娠74例,异位妊娠发生率为4.67%;异位妊娠类型中输卵管妊娠71例,占总异位妊娠的95.95%。新鲜胚胎移植周期组异位妊娠发生率(5.41%)显著性高于冷冻胚胎复苏移植(frozing embryo transfer,FET)周期组(2.35%)(P<0.05)。移植深度距离宫底>1.2 cm时异位妊娠发生率显著性低于移植深度0.8~1.2 cm组。结论:IVF-ET助孕技术中异位妊娠发生率较自然妊娠过程中高;输卵管因素、促排卵药物的应用以及胚胎移植的深度是异位妊娠发生的主要影响因素。     

Placental growth factor (PlGF) as an angiogenic/inflammatory switcher: lesson from early pregnancy losses

Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may shift to severe inflammation and cause tissue damages which could lead to early pregnancy losses. Downregulation of PlGF has also been reported in pregnancy complications. In this review, we discussed the role of PlGF in embryo implantation failure and early pregnancy loss and also possible mechanisms regarding the role of PlGF in angiogenic/inflammatory switching in early pregnancy losses. Furthermore, we summarized the effects of various compounds on PlGF expression and briefly talked about its therapeutic potential that may be an opportunity for prevention of pregnancy loss.