The role of leukemia inhibitory factor in tubal ectopic pregnancy

Introduction

Ectopic pregnancy is unique to humans and a leading cause of maternal morbidity and mortality. The etiology remains unknown however factors regulating embryo implantation likely contribute. Leukemia inhibitory factor (LIF) has roles in extravillous trophoblast adhesion and invasion and is present in ectopic implantation sites. We hypothesised that LIF facilitates blastocyst adhesion/invasion in the Fallopian tube, contributing to ectopic pregnancy.

Methods

We immunolocalised LIF receptor (R) in tubal ectopic pregnancy (N = 5). We used an oviduct cell line (OE-E6/E7) to model Fallopian tube epithelial cells and a trophoblast spheroid co-culture model (HTR-8/SVneo cell line formed spheroids) to model blastocyst attachment to the Fallopian tube. We examined LIF signaling pathways in OE-E6/E7 cells by Western blot. The effect of LIF and LIF inhibition (using a novel LIF inhibitor, PEGLA) on first-trimester placental outgrowth was determined.

Results

LIFR localised to villous and extravillous trophoblast and Fallopian tube epithelium in ectopic pregnancy. LIF activated STAT3 but not the ERK pathway in OE-E6/E7 cells. LIF stimulated HTR-8/SVneo spheroid adhesion to OE-E6/E7 cells which was significantly reduced after PEGLA treatment. LIF promoted placental explants outgrowth, while co-treatment with PEGLA blocked outgrowth.

Discussion

Our data suggests LIF facilitates the development of ectopic pregnancy by stimulating blastocyst adhesion and trophoblast outgrowth from placental explants. Ectopic pregnancy is usually diagnosed after 6 weeks of pregnancy, therefore PEGLA may be useful in targeting trophoblast growth/invasion.

Conclusion

LIF may contribute to the development of ectopic pregnancies and that pharmacologically targeting LIF-mediated trophoblast outgrowth may be useful as a treatment for ectopic pregnancy.     

LIF及其抗体对小鼠胚胎着床影响的体外研究

目的 :研究外源性白血病抑制因子 (LIF)及其抗体对小鼠胚胎着床的影响。方法 :将妊娠 4d的小鼠胚胎种植于已建立的子宫内膜体外模型上 ,观察不同浓度的LIF及其抗体对小鼠胚胎的粘附、植入及扩展情况。并用RT PCR法测定子宫内膜上皮细胞整合素β3的变化。结果 :不同浓度的LIF促进了胚胎的粘附 (P <0 .0 5 ) ,胚胎的扩展率降低。加入LIF抗体 (5 ,1 0 μg/ml)降低了胚胎的粘附率 (P <0 .0 5 ) ,同时LIF对整合素β3的表达有明显的促进作用 (P <0 .0 1 ) ,加入抗体后整合素β3的表达降低。结论 :LIF可能通过上调整合素β3的表达促进胚胎的粘附和植入     

三维超声测定子宫内膜容积预测IVF-ET结局

目的评价三维(3D)超声测定子宫内膜容积在预测体外受精-胚胎移植(ⅣF-ET)结局中的作用.方法对124例行ⅣF-ET的患者在HCG注射当天进行超声测定子宫内膜的厚度和容积.结果妊娠组(48例)和未妊娠组(76例)在HCG注射当天测得的子宫内膜厚度、内膜容积、子宫容积两组间无统计学差异(P＞0.05).子宫内膜容积和厚度的ROC曲线下面积分别为0.532和0.523.子宫内膜容积＜2.0ml的5例患者,无一例发生妊娠.结论子宫内膜容积和子宫内膜厚度不能预测ⅣF-ET结局.但子宫内膜容积测定可指导是否行ET.     

Use of the total motile sperm count to predict total fertilization failure in in vitro fertilization

OBJECTIVE: To evaluate the capacity of baseline characteristics and total motile sperm count (TMC) to predict total fertilization failure (TFF) in patients undergoing IVF. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Eight hundred ninety-two couples with a total of 1,569 consecutive IVF cycles. INTERVENTION(S): Prewash and postwash TMC during fertility workup and at the time of ovum pickup (OPU). MAIN OUTCOME MEASURE(S): Analysis of logistic regression and the receiver operating characteristic curve were used to determine which variables could be used to predict TFF. RESULT(S): The area under the curve (AUC) for prewash TMC during fertility workup was 0.72, similar to a combination of pre- and postwash TMC. At the time of OPU, both pre- and postwash TMC had an AUC of 0.73. A model based on selected baseline characteristics (male age, number of IVF cycles, indication for IVF, and prewash TMC during fertility workup) had an AUC of 0.75. A model at the time of OPU, including the number of oocytes, had an AUC of 0.80. CONCLUSION(S): The use of both models, one before start of the IVF cycle and one at the time of OPU, allows an accurate prediction of the chance of TFF and is useful in counseling patients on whether to opt for IVF or ICSI.     

几种药物对子宫内膜容受性影响的研究

子宫内膜容受性是子宫内膜接受胚胎着床的一种综合状态,与胚胎植入率及妊娠率密切相关。随着辅助生殖技术的发展,促排卵药物应用的成熟,对不孕症的诊治也上升到新的高度,提高胚胎植入率及妊娠率成为关键。控制性超排卵药物会影响子宫内膜的生长,改变子宫内膜容受性。通过总结几种中西药物对子宫内膜容受性的影响,以期为提高辅助生殖技术的成功率提供参考。     

Ovarian pregnancy after in vitro fertilization

We report a rare ovarian pregnancy after in vitro fertilization and transcervical embryo transfer. Ultrasound guidance of embryo transfer does not eliminate the risk of this potentially lethal complication.     

The effect of medical clowning on pregnancy rates after in vitro fertilization and embryo transfer

This experimental prospective quasi-randomized study examining the impact of a medical clowning encounter after embryo transfer (ET) after in vitro fertilization (IVF) found that the pregnancy rate in the intervention group was 36.4%, compared with 20.2% in the control group (adjusted odds ratio, 2.67; 95% confidence interval, 1.36-5.24). Medical clowning as an adjunct to IVF-ET may have a beneficial effect on pregnancy rates and deserves further investigation.     

Comparison of the efficacy and safety of two formulations of micronized progesterone (Ellios and Utrogestan) used as luteal phase support after in vitro fertilization

OBJECTIVE: To compare the efficacy and the tolerability of two different vaginal formulations of micronized progesterone, Ellios and Utrogestan, used for luteal phase support after an in vitro fertilization (IVF) cycle. DESIGN: Cohort study. SETTING: Fertility center in a university hospital. PATIENT(S(: One hundred twenty-three women who underwent IVF/intracytoplasmic sperm injection (ICSI) stimulated cycles from October 1998 to March 2000, who had at least six follicles of > or =14 mm on the day of hCG administration. INTERVENTION(S): Patients received Ellios pessaries (2 times 200-mg pessary/day) or Utrogestan capsules (2 x 100-mg capsules, two times a day). Progesterone was administered from the day of oocyte pickup (day 0) until menses or up to 10 weeks in pregnant patients. MAIN OUTCOME MEASURE(S): Progesterone levels, pregnancy rate, and tolerability tested by patient questionnaire. RESULT(S): The progesterone levels on days 0, 9, 16 were not statistically different between the two formulations. The pregnancy rate were similar in groups 1 and 2 (25.5% vs. 18.6%), whereas tolerance was significantly better in group 1 versus group 2 (vaginal discharge: 43% vs. 82%). CONCLUSION(S): The efficacy of the two formulations of progesterone is comparable, although the patient tolerance for Ellios is better.     

几种药物对子宫内膜容受性影响的研究

子宫内膜容受性是子宫内膜接受胚胎着床的一种综合状态,与胚胎植入率及妊娠率密切相关。随着辅助生殖技术的发展,促排卵药物应用的成熟,对不孕症的诊治也上升到新的高度,提高胚胎植入率及妊娠率成为关键。控制性超排卵药物会影响子宫内膜的生长,改变子宫内膜容受性。通过总结几种中西药物对子宫内膜容受性的影响,以期为提高辅助生殖技术的成功率提供参考。     

Endometrial biopsy at the time of embryo transfer: Correlation of histological diagnosis with therapy and pregnancy rate

Biopsy to assess the state of the endometrium was performed in 27 patients prior to embryo transfer. Of the 24 classifiable biopsies, 15 (63%) were secretory and 9 (37%) were proliferative. In the nine women in the latter category, in vitro fertilization (IVF) resulted in four pre-clinical pregnancies and five failures. In the 15 women with secretory endometrium there were 11 pregnancies (3 preclinical, 6 abortions, and 2 term). This study demonstrates that endometrial biopsy at the time of embryo transfer does not exclude viable pregnancy. The presence of a proven secretory endometrium may also be an important factor in determining the successful outcome of IVF.     

Psychological status of in vitro fertilization patients during pregnancy: a longitudinal study

Objective: To determine whether women who get pregnant as a result of IVF differ psychologically from pregnant women who conceived naturally.

Design: Prospective, longitudinal study.

Setting: Healthy volunteers from outpatient infertility and obstetrics practices.

Patient(s): Seventy-four women who became pregnant via IVF and 40 women conceiving without medical intervention.

Intervention(s): Subjects completed self-report questionnaires about demographic and reproductive history, rewards and concerns of pregnancy, self-esteem, marital adjustment, depressive symptoms, and anxiety at 12 and 28 weeks’ gestational age.

Main Outcome Measure(s): Self-esteem, depression, and anxiety scores.

Result(s): There were no significant differences between groups on any of the outcome measures assessing psychological status at the two assessment times. Differences were found on specific items assessing the rewards and concerns of pregnancy. Within-group changes over time indicated that IVF women, not controls, showed an increase in self-esteem and a decrease in anxiety during pregnancy.

Conclusion(s): Pregnant IVF women are similar psychologically to women who become pregnant naturally on dimensions of self-esteem, depression, and anxiety at 12 and 28 weeks’ gestational age. The IVF group, not controls, reported improved self-esteem and decreased anxiety as the pregnancy progressed.     

Serum human chorionic gonadotropin measurements may predict pregnancy outcome and multiple gestation after in vitro fertilization

OBJECTIVE: To predict pregnancy outcome and multiple gestation using a common parameter by which hCG values are made comparable independently of the day of blood sampling.DESIGN: Retrospective study.SETTING: University-based IVF program.PATIENTS: One hundred twenty IVF pregnancies conceived between November, 1995 and August, 1999.INTERVENTIONS: None.MAIN OUTCOME MEASURES: Early pregnancy loss (preclinical and first trimester abortions, ectopic pregnancies) or ongoing pregnancies (singleton and multiple deliveries, second trimester abortions). Day 11 hCG levels were calculated assuming an exponential increase of hCG values in early pregnancy. Receiver-operating characteristic analysis was used to determine cut-off levels with the best sensitivity and specificity for the prediction of pregnancy outcome.RESULTS: Serum hCG levels in the group of early pregnancy loss were significantly lower than in ongoing pregnancies. A cut-off level of 50 IU/L predicts pregnancy outcome with a sensitivity of 75% and a specificity of 81%, while an hCG value >135 IU/L predicts a multiple ongoing pregnancy with a sensitivity of 80% and a specificity of 88%.CONCLUSION: After IVF, early pregnancy loss or multiple gestation may be predicted with high sensitivity and specificity by using cut-off values of serum hCG derived from two measurements independently of the day of blood sampling.     

Pelvic abscess complicating an in vitro fertilization pregnancy and review of the literature

INTRODUCTION: In vitro fertilisation has become a very common procedure in the infertility practice due to both accessibility and good success rates. DISCUSSION: Complications, however, are constant reminders that no procedure is totally safe. In this paper, we present a case of IVF pregnancy that presented with pelvic abscess, and despite two laparotomies the triplet pregnancy was lost at 22 weeks gestation. CONCLUSION: This case highlights the fact that the progression of pelvic infection in pregnancy can be slow.     

Hysteroscopy in women with implantation failures after in vitro fertilization: Findings and effect on subsequent pregnancy rates

ObjectiveTo evaluate the effect of hysteroscopic endometrial cavity evaluation and management prior to IVF in patients with repeated implantation failures.DesignRetrospective cohort study.SettingPrivate assisted reproduction unit.PatientsOne hundred and thirty-two patients with a history of repeated implantation failures despite the transfer of at least three good-quality embryos per transfer.InterventionsHysteroscopy (diagnostic or operative, as appropriate) to evaluate the endometrial cavity followed by repeated IVF/ICSI.Main outcome measuresIncidence of abnormal hysteroscopic findings and the clinical pregnancy rate (CPR) in subsequent IVF cycles.ResultsIn all, 38% of the study population had abnormal hysteroscopic findings and 22.2% of women with abnormal hysteroscopic findings showed a significantly increased CPR in subsequent IVF cycles.ConclusionWomen with repeated implantation failures after IVF have a remarkably high possibility of achieving pregnancy after hysteroscopic evaluation and management of endometrial cavity pathology.