Early pregnancy wastage in IVF (in vitro fertilization) patients

Human in vitro fertilization is characterized by a low of ficiency of implantation. Possible mechanisms for pregnancy loss are discussed. Embryo viability or quality, abnormal implantation, and delayed or absent corpus luteum rescue may all play a role in pregnancy wastage. Defining the possible mechanism for these losses may allow hormonal treatment to correct specific abnormalities.Presented in part at the International Meeting on Pregnancy Loss in Tel Aviv, Israel, April 1989.     

Risk factors for ectopic pregnancy afterin vitro fertilization and embryo transfer

Purpose To find the incidence of ectopic pregnancy (EP) in patients who conceived in the IVF-ET program, and risk factors affecting the occurrence of EP.Methods We analyzed the effects of the indication for IVF, type of ovarian stimulation (hMG + hCG vs. GnRH + hMG + hCG), type of embryo transfer (transcervical intratubal, intrauterine in chest-knee position and intrauterine in lithotomy position) and number of embryos transferred on the occurrence of EP. EP was treated by laparotomy, prostaglandin E ₂ or laparoscopic surgery.Results In 7991 stimulated and 92 natural cycles treated in the Ljubljana IVF-ET program between May 1983 and June 1994 we achieved 1059 pregnancies, of which 44 were ectopic (incidence 4.1%), the main risk being tubal factor infertility. There were 38 (86.3%) tubal, 3 (6.8%) heterotopic, 1 (2.4%) ovarian, and 2 (4.5%) cornual EP. In two patients multiple tubal EP occurred (1 twin, 1 triplet). Forty-two patients (95.4%) had tubal factor infertility, 1 (2.3%) unexplained, and 1 (2.3%) patient had male factor. The incidence of EP in patients with tubal infertility was 5.4%, in patients with unexplained infertility 2.0% and in those with male factor 0.9%. There appeared to be no correlation between the two superovulatory methods. With transcervical intrauterine ET the incidence of EP was 0 of 5 clinical pregnancies (CP); with intrauterine in chest-knee position it was 26 (3.5%) of 738 CP; with intrauterine in lithotomy position it was 17 (5.4%) of 316 CP. The difference between the two types of intrauterine ET is not statistically significant. The incidence of EP did not correlate with the number of embryos transferred. The average initial values of beta hCG performed 17 days after ET were significantly lower in patients with EP than in those with normal singleton pregnancy (157±143 mIU/ml vs. 408±148 mIU/ml).Conclusions EP can complicate the IVF procedure. The main risk factor is tubal infertility with or without previous tubal surgery. The low initial value of beta hCG has a strong predictive value in the diagnosis of EP.Presented at the IXth World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, April 3–7, 1995, Vienna, Austria.     

Limiting multiple pregnancy in in vitro fertilization/embryo transfer (IVF-ET) cycles

Purpose: Our purpose was to assess how the number of embryos transferred can be adjusted to limit multiple gestations. Methods: A retrospective analysis of 535 consecutive embryo transfers for the years 1991–1993 was conducted. Results: Fewer than three embryos were associated with a low pregnancy rate. Pregnancy rates were highest in women less than 35 when four or more embryos were transferred. With four or more embryos, multiple gestation pregnancy correlated with the number of high-quality embryos transferred. The risk of triplets and quadruplets was greatest for women less than 40. Conclusions: Multiple-embryo transfer carries a risk of plural gestation. The risk of multiple pregnancy cannot be eliminated without decreasing the pregnancy rate. The risk of high-order multiple pregnancy was best correlated with the number of good-quality embryos transferred. While all are at risk, patients younger than 40 were at highest risk.     

Diagnosis of ectopic pregnancy after in vitro fertilization and embryo transfer

Objective: The combination of transvaginal sonography and serum hCG measurement is reliable in the diagnosis of ectopic pregnancy (EP) in spontaneous pregnancies. In patients who became pregnant through IVF-ET, transfer of multiple embryos after IVF could be responsible for the different performance of these tests. We evaluated the discriminative capacity of transvaginal sonography in combination with hCG measurement in the diagnosis of EP after IVF-ET.

Design: Prospective cohort study.

Setting and Patient(s): Consecutive patients, pregnant through IVF-ET, who presented with clinically suspected EP.

Intervention(s): Transvaginal sonography, serum hCG measurement at 6, 9, and 15 days after ET and after a negative transvaginal sonography.

Main Outcome Measure(s): Ectopic pregnancy confirmed at laparoscopy.

Result(s): Between September 1993 and May 1996, 86 women were included in the study, of whom 24 had an EP. Transvaginal sonography identified 46 intrauterine pregnancies and 5 EPs, but serum hCG could not diagnose EPs in patients in whom transvaginal sonography did not show a gestational sac. Serum hCG measurement 9 days after ET could identify pregnancy failure with 100% specificity at a cut-off value of 18 IU/L, but it could not identify patients with EP with enough certainty to justify immediate treatment.

Conclusion(s): We recommend single serum hCG measurement 9 days after ET to discriminate between viable and nonviable pregnancies. Transvaginal sonography can be postponed until 5 weeks after ET, except for patients with abdominal pain and/or vaginal bleeding, or patients with a serum hCG level of <18 IU/L.     

高催乳素血症患者体外受精-胚胎移植妊娠结局的临床分析

目的分析无症状的高催乳素血症（hyperprolactinemia,HPRL）患者接受体外受精-胚胎移植（IVF-ET）助孕治疗时的妊娠结局。方法回顾性分析217例确诊高催乳素血症患者接受IVF-ET助孕治疗的临床资料,同期121例输卵管因素行IVF而血清催乳素水平正常的患者为对照组,比较分析卵泡数、获卵数、受精率、临床妊娠率、胚胎着床率及妊娠结局等。结果两组间促性腺激素使用刺激时间、促性腺激素用量、获卵数、HCG日内膜厚度、受精率差异无统计学意义（P〉0.05）。高催乳素血症患者的临床妊娠率及着床率显著低于对照组（P〈0.05）。血清催乳素水平低于50 ng/ml的患者,经多巴胺受体激动剂治疗进入IVF周期前血清泌乳素水平高于25 ng/ml组,与血清催乳素水平正常组比较,获卵数、受精率、临床妊娠率、着床率和妊娠结局差异无统计学意义（P〉0.05）。结论高催乳素血症会对IVF结局产生不利影响。血清催乳素水平低于50 ng/ml可以进入IVF周期,不影响促排卵和妊娠结局。     

Relationship among serum levels of luteinizing hormone,estradiol, and progesterone during follicle stimulation and results of in vitro fertilization and embryo transfer (IVF-ET)

Eighty-eight IVF-ET cycles were classified into four groups according to the results of IVF-ET (Group A—conceptional cycles, 10 cycles; Group B—cycles with cleaved oocytes, 58 cycles; Group C—cycles with fertilized oocytes, 9 cycles; Group D—cycles without fertilization, 11 cycles). Serum luteinizing hormone (LH), estradiol (E ₂ ), and progesterone (P) levels during follicle stimulation were studied in these groups. Patients participated in our IVF-ET program due to irreparable tubal damage. Follicle development was stimulated with a clomiphene—human menopausal gonadotropin (hMG)—human chorionic gonadotropin (hCG) regimen. Group C showed a low E ₂ response to follicle stimulation. Groups B and D showed significantly higher serum P levels on day 0 (the day of hCG injection) than Group A (Group A, 0.73 ± 0.11, vs Groups B and D, 1.43 ± 0.15 and 2.17 ± 0.42 ng/ml; P <0.01). The effects of serum P and LH levels on the fertilization and pregnancy rates were studied. The pregnancy rate was not affected by the serum LH level but was only 2.7% in cycles in which serum P was 1.2 ng/ml on day 0, which was significantly lower than that in cycles in which serum P was <1.2 ng/ml on day 0 (19.1%) (P <0.05). The fertilization rate was significantly lower in the cycles with higher levels of serum P and/or LH than in cycles in which serum P was <1.2 ng/ml and serum LH was normal (50.5 vs 78.8%; P <0.01). These findings suggest that the serum P level, but not the LH level, during follicle stimulation is closely related to the achievement of pregnancy.     

Relationship between the day of embryo transfer and the outcome in human in vitro fertilization and embryo transfer

Purpose To clarify the optimal date of embryo transfer (ET), we retrospectively analyzed the relationship between the day of ET and the outcome in human in vitro fertilization and embryo transfer (IVF-ET).Method Of a total of 307 human IVF-ET cycles performed at Kyoto University Hospital between January 1990 and March 1994, we focused on 207 cases of IVF-ET cycles in which two or three good-quality embryos were transferred. These 207 IVF-ET cycles consisted of 54 Day 2 ET cycles, 79 Day 3 ET cycles, 46 Day 4 ET cycles, and 28 Day 5 ET cycles. We compared the pregnancy and live-birth (plus ongoing pregnancy) rates among these four ET groups.Results The pregnancy rates of ET on Days 2 to 4 were not significantly different, whereas Day 5 ET produced a significantly lower pregnancy rate (Day 2, 29.6%; Day 3, 32.9%; Day 4, 30.4%; Day 5, 10.7%). Similar results were obtained for the live-birth (plus ongoing pregnancy) rates (Day 2, 20.3%; Day 3, 18.9%; Day 4, 17.9%; Day 5, 7.1%).Conclusions These results suggest that the day of ET does not fundamentally affect the pregnancy rate in human IVF-ET provided that transfer is made before Day 5.     

体外受精 - 胚胎移植后异位妊娠的危险因素、诊断及治疗

目的　探讨体外受精 -胚胎移植 (IVF-ET)后异位妊娠 (EP)的危险因素、诊断及治疗方法。方法　对我院 1992年 10月～ 2 0 0 2年 6月接受体外受精-胚胎移植治疗 (包括单精子胞浆内注射 ,ICSI)后 82 1例临床妊娠中 38例异位妊娠进行回顾性分析。结果　IVF -ET后异位妊娠的发生率 4 6 % ,多胚胎不同部位妊娠(HP)的发生率 0 6 %。异位妊娠组取卵数明显多于对照组。单因素分析发现异位妊娠史、盆腔炎性疾病 (PID)史是IVF-ET后异位妊娠的危险因素。结论　盆腔炎性疾病史、异位妊娠史是IVF -ET后异位妊娠的高危因素。胚胎移植后妇女激素水平可能与异位妊娠的发生相关 ,但需进一步的研究证实。早期诊断和微创性治疗 ,减少异位妊娠的并发症和死亡率     

Delayed embryo implantation following in vitro fertilization and embryo transfer (IVFET)

Purpose: Our goal was to compare serum human chorionic gonadotropin (hCG) levels in singleton pregnancies achieved following IVFET with those achieved following spontaneous conception. Results: The mean serum hCG level of patients who became pregnant following IVFET lagged 1.5 days behind that of patients who became pregnant spontaneously. Conclusions: The use of gonadotropin releasing hormone analogue as part of the stimulation protocol leading to egg retrieval and IVFET results in a delay in embryo implantation.     

Heterotopic pregnancy following in vitro fertilization and embryo transfer: 12 cases report

Objective  To evaluate the incidence, predisposing factors, early diagnosis and treatment options of heterotopic pregnancy (HP) following in vitro fertilization and embryo transfer (IVF-ET) procedure. Methods  A retrospective review study was performed to identify the HP cases after IVF-ET at the Reproductive Centre in Guangdong Women and Children’s Hospital in China between the years of 2002–2007. Results  Twelve out of 1,476 pregnancies (0.81%) were diagnosed for HP, of which nine patients elected for exploratory salpingectomy, two patients received selective fetal reduction by embryo aspiration under ultrasound guidance, and one patient opted for expectant treatment. Postoperatively, four intrauterine pregnancies were continued to develop until term while two were delivered at 35 weeks of gestation. The achievement ratio of continuous pregnancy was 66.7% (6/9). Conclusion  The incidence of HP is increasing due to the widespread use of assisted reproductive technology. An early transvaginal sonography performed by experienced radiologist/radiographer is considered to be essential and beneficial in establishing early diagnosis of HP. Both salpingectomy and selective fetal reduction by embryo aspiration can be administered as one of the effective therapies for HP with the optimal outcome of intrauterine pregnancy.     

Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer

OBJECTIVE: To examine the effect of beta-cyclodextrin piroxicam treatment for priming of the uterus on the pregnancy outcome of IVF-embryo transfer (ET) programs. DESIGN: Prospective, randomized, double-blinded placebo-controlled clinical study. SETTING: Large urban medical center. PATIENT(S): One hundred eighty-eight consecutive cycles of fresh IVF-ET and 78 cycles of frozen-thawed ET. The patients underwent IVF because of tubal, male infertility, unexplained, or endometriosis factors. They were randomly divided into treatment and control groups. INTERVENTION(S): In the treatment group, 94 cycles in fresh ET and 39 cycles in frozen-thawed ET the patients received an oral dose of 10 mg of piroxicam. In the control group, the same number cycles corresponding to the treatment group were treated with placebo. Both groups started piroxicam or placebo treatment 1-2 hours before ET. Patients and staff were blinded to the treatment. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and pregnancy rate (PR). RESULT(S): Piroxicam increased significantly IR (18.7%) and PR (46.8%) compared to the control group (8.6% and 27.6%, respectively) in fresh cycles. With the exception of an unexplained factor, patients with the tubal, male infertility, or endometriosis factor had significantly higher PR in the treatment group compared to the control group. The beneficial effect of piroxicam was found in patients less than 40 years old, but was not found in patients more than 40 years. In frozen-thawed cycles, there were statistically significant differences between the treatment group and the control group in IR (9.4% vs. 2.3%) and PR (25.6% vs. 7.7%), respectively. CONCLUSION(S): Our study showed that piroxicam increases IR and PR after IVF-ET in both fresh and frozen-thawed ET cycles. The beneficial effect seems to be more remarkable in patients less than 40 years old with tubal, male infertility, or endometriosis factors. These results suggest that piroxicam treatment before ET is very effective in the priming of a uterus suitable for embryo implantation. This is the first study to investigate the possible consequence of piroxicam for improving the PR after IVF-ET.     

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。     

体外受精-胚胎移植术后宫角妊娠合并宫腔粘连1例病例报告与文献回顾

目的介绍1例行体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)、出现宫角妊娠合并宫腔粘连并成功活产的病例。方法对本院1例重度宫腔粘连分解术后行IVF-ET病例发生宫角妊娠合并宫腔粘连的临床资料进行分析,并对相关文献进行系统性回顾。结果该病例于孕36+3周行子宫下段剖宫产术,成功活产一男婴。结论宫角妊娠是可能危及生命的妇产科急症,但对于妊娠困难的患者,严密监测及期待治疗可获得良好的妊娠结局。     

体外受精-胚胎移植术后单胎妊娠子痫前期发病特征分析

目的探讨体外受精-胚胎移植（IVF-ET）术后妊娠发生子痫前期的临床特征。方法回顾性分析2008年1月至2012年12月IVF-ET术后单胎妊娠子痫前期35例（IVF-ET组）和单胎自然妊娠子痫前期126例（自然妊娠组）患者的临床表现、辅助检查及妊娠结局。结果 IVF-ET组子痫前期的发生率为13.13%（211/1607）,与自然妊娠组（4.83%,844/17 483）比较,差异有统计学意义（P〈0.05）;IVF-ET组子痫前期的平均发病时间为妊娠（31.67±6.63）周,自然妊娠组为（33.76±4.46）周,两组比较,差异有统计学意义（P〈0.05）;IVF-ET组分娩孕周为（34.79±5.19）d,自然妊娠组为（34.27±4.30）d,两组比较,差异无统计学意义（P〉0.05）;IVF-ET组前置胎盘发生率为14.29%（5/35）,与自然妊娠组（3.97%,5/126）比较,差异有统计学意义（P〈0.05）;IVF-ET组平均住院时间[（20.68±14.61）d]与自然妊娠组[（11.96±7.14）d]比较,差异有统计学意义（P〈0.05）;既往妊娠史中,IVF-ET组异位妊娠和自然流产发生率分别为8.57%（3/35）和20.00%（7/35）,自然妊娠组分别为0（0/126）和6.35%（8/126）,两组比较,差异有统计学意义（P〈0.05）。结论 IVF-ET术后妊娠子痫前期的发病率高于自然妊娠,发病时间早,前置胎盘发生率增高。在既往史中,IVF-ET组自然流产与异位妊娠的发生率较高。IVF-ET术后子痫前期患者经过适当的临床干预及期待治疗,有可能延缓子痫前期的进展,延长孕周,降低孕妇并发症的发生,改善妊娠结局。     

Epidural anesthesia in anin vitro fertilization and embryo transfer program

Objectives To investigate the potential advantages of epidural anesthesia in an in vitro fertilization and embryo transfer program.Study Design Between January 1991 and December 1992, 148 infertile patients underwent transvaginal ultrasound guided oocyte retrieval. A total of 44 patients (group A) had 50 retrievals under epidural anesthesia, and 104 patients (group B, control group) 112 retrievals under intravenous sedation (propofol) with mask-assisted ventilation (nitrous oxide).Results In group A satisfactory anesthesia was achieved in 49 of the 50 cases (98%); one patient required additional intravenous administration of propofol owing to extreme anxiety. No complications were observed. Adversely, in group B nausea was observed in 16 cases (14%) and nausea and vomiting in 7 cases (6%). In group A the fertilization, cleavage and pregnancy rates were 67.2%, 92% and 20% respectively, while in group B the rates were 69.3%, 93% and 19.6% respectively; the differences are not statistically significant.Conclusions Epidural anesthesia is an effective method for transvaginal oocyte retrieval but does not improve the treatment outcome as compared to an intravenous sedation with mask-assisted ventilation using propofol and nitrous oxide.