Ectopic pregnancies after in vitro fertilization and embryo transfer

Objective Our objective was to analyze the risk factors, stimulation characteristics, and future fecundity of patients with ectopic pregnancies after in vitro fertilization (IVF).Methods We retrospectively evaluated all cases of ectopic pregnancy occurring between January 1989 and March 1993 (Cornell series 1 to 17). A case-control group of intrauterine pregnancies was used for comparison of the stimulation and transfer characteristics.Results Twenty-seven of 1123 pregnancies (2.4%) were ectopic, following 2812 fresh IVF embryo transfers, while 8 of 105 pregnancies (7.6%) were ectopic, following 405 frozen-thawed embryo transfers. Tubal factor was the cause of infertility in the majority (85.7%) of ectopic pregnancies. No difference was found between the ectopics and the matched controls in stimulation and transfer characteristics. Thirty ectopic pregnancies were ampullary, two were interstitial, two were cervical, and one was heterotopic. Twenty of the patients subsequently underwent 29 IVF attempts, with a pregnancy rate of 41.4% per transfer.Conclusions Ectopic pregnancy after IVF appears to be related to preexisting tubal pathology; embryo transfer of cryopreserved thawed embryos in a natural cycle may result in a higher ectopic rate in these patients; in subsequent IVF cycles the intrauterine pregnancy rate of these patients is not decreased.     

克罗米芬在体外受精-胚胎移植方案中的应用

克罗米芬(CC)应用于体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)的促排卵方案中,比常规方案更简单、方便、经济,可重复性高。但CC对子宫内膜的负面影响,使其在IVF中的应用受到限制,而针对这些负面影响采取的改善措施是否有效,也存在争议。CC应用于微刺激方案中与常规促排卵方案比较,减少了Gn用量,缩短了Gn天数,减少了卵巢过度刺激综合征(OHSS)的发生,在微刺激方案中,促排卵后期加用CC能够更好地改善抗雌激素作用及抑制LH峰,降低周期取消率,获得较多的卵子及较好的子宫内膜厚度。     

In vitro fertilization and embryo transfer during natural cycles

OBJECTIVE: To report the results of in vitro fertilization and embryo transfer (IVF/ET) performed during natural cycles. STUDY DESIGN: A prospective clinical study. RESULTS: Thirty-two cycles were started in 19 patients who had regular ovulatory cycles and tubal factors or unexplained infertility only as the cause of infertility. Egg collection was performed in 12 cycles, and four pregnancies resulted from ET in eight cycles. The pregnancy rates were 12.5% per cycle initiated, 33.3% per retrieval cycle and 50% per transfer. CONCLUSION: Natural cycle IVF/ET offers a low-cost alternative to patients with infertility.     

Effect of various factors on in vitro fertilization (IVF) and embryo transfer in the human in clomiphene/hMG/hCG stimulated cycles

In the present study we tried to analyse data obtained on the occasion of an in vitro fertilization programme at the department of obstetrics and gynecology of the University of Kiel, to extract some of the important factors, because their positive or negative influence on the success of extracorporal insemination, embryo transfer and implantation has not been clearely defined till now and to value their concern. Between July 1982 and February 1983 105 sterile patients with ovulatory menstrual cycles have been treated by the technique of in vitro fertilization and embryo transfer, successively. Follicular growth was stimulated by 150 mg clomiphen daily from 3rd to 7th day and application of 225 IU hMG on 6th, 8th and 10th day. Finally ovulation was timed 36 hours before follicular puncture by 5000 IU hCG. In 24 per cent endogenous LH peak could be observed. In 86 per cent of the 80 patients exactly timed one oocyte was to be found minimally. In 68 per cent of these patients after all an embryo transfer was done (24 times one embryo, 13 times two, 9 times three and once four embryos). 89% of the embryos have been transfered as 4-or 8-cell stage, only 11 per cent as two cell stage. Transfer took place 48 to 50 hours following insemination. There was no correlation between the maturity classified morphologically of the oocytes and the diameter of their follicles. The speed of development of the embryos was not correlated with the size of their follicles. too. In 60-70 per cent of all cases, in which an embryo transfer was possible, husbands had normal spermiogram. The percentage of unfertilised oocytes following insemination using non-optimal sperma was increased in all types of cycles, additionally there was a reduction of the developing speed of resulting embryos. Doubtless two the four pregnancies resulted after insemination using sperma of less quality. The conjugation rate is said to be not correlated directly with the exactness of timing of the application of hCG with reference to follicular maturity, but in all pregnancies hCG was injected simultaneously with the peak of estradiol.     

Ultrasonic assessment of endometrial changes in stimulated cycles in an in vitro fertilization and embryo transfer program

Four distinct patterns in the ultrasonic appearance of preovulatory endometrium can be identified and described in patients undergoing stimulated cycles in an in vitro fertilization program. Ultrasonically, this endometrial response can be seen as a quantitative change in thickness and a qualitative change in gray-scale appearance or reflectivity. The application of this additional parameter of endometrial assessment together with the conventional measurement of follicular diameter as a means of optimally timing oocyte collection has been associated with a reduction in the preoperative ovulation rate from 10.9 to 3.2%, an increase in the fertilization rate from 59.2 to 82.5%, and in a pregnancy rate per embryo transfer of 20.5% in our program without the use of hormonal assays.     

Monitoring gonadotropin-stimulated cycles for in vitro fertilization and embryo transfer

One hundred fifty-one cycles stimulated with human menopausal gonadotropin (hMG) and/or folliclestimulating hormone (FSH) were analyzed retrospectively to determine the relationship of the monitoring parameters used: serum estradiol (E₂), transvaginal sonographic follicular size, and peripheral biologic estrogen response, with harvests and pregnancies resulting from in vitro fertilization and embryo transfer. Mean ± SE serum E₂ levels were higher on the day of human chorionic gonadotropin (hCG) administration in the miscarriage group (689.4±27.5 pg/ml) than in the nonpregnant group (527.7±25.8 pg/ml) (P=0.018) and highest in the ongoing pregnancy group (734.6±66.5 pg/ml) (P=0.003). When two or more preovulatory oocytes (preovs) were retrieved, the mean E₂ levels were higher (622.3±27.3 pg/ml) than if zero or one preov was retrieved (378.4±43.5 pg/ml) (P=0.001). The mean diameter of the two largest follicles at the time of hCG administration was significantly greater (14.7 mm) in the group with two or more preovs retrieved than in the group with zero or one preov (13.3 mm) (P=0.001). The relative probability of achieving a pregnancy was best predicted by the presence of two follicles16 mm in diameter on transvaginal ultrasound examination and was 1.63 times greater than that of all patients in this series.     

Delayed appearance of plasmatic chorionic gonadotropin in pregnancies after in vitro fertilization and embryo transfer

The detection of pregnancy through the rise of human chorionic gonadotropin hormone secretion, on maternal plasma level, has been studied in normally developed pregnancies following in vitro fertilization and embryo transfer (IVF-ET), and compared with two other groups of pregnancies, the first group being pregnancies following artificial insemination with donor semen (AID) in spontaneous cycles ("AID group") and the second group being pregnancies following in vivo fertilization in a stimulated cycle ("stimulated group"). The day of human chorionic gonadotropin detection level significant for pregnancy (Dd) has been first defined and then determined for each pregnancy. Thereafter, mean levels for Dd (Dd) have been compared for each pregnancy group. It has been found that in pregnancies following IVF-ET, Dd is 12.05 +/- 0.8 days after ovulatory stimulus, which is delayed in comparison with spontaneous cycle pregnancies (Dd = 9.5 +/- 1.0) and with stimulated cycle pregnancies (Dd = 8.0 +/- 1.5). The hypothesis to explain this observation is then discussed.     

Altered follicular development in clomiphene citrate versus human menopausal gonadotropin-stimulated cycles for in vitro fertilization

The pattern of periovulatory and luteal phase serum estradiol (E2) and progesterone (P) as well as follicular fluid (FF) E2, P, androgen, gonadotropin, and prolactin concentrations of eight women undergoing clomiphene citrate (CC)/human chorionic gonadotropin (hCG) stimulation and eight women undergoing human menopausal gonadotropin (hMG)/hCG stimulation of follicular development for the purpose of in vitro fertilization were compared. Ovulation was induced with either a 5-day course of CC (100 mg/day beginning on day 5 of the cycle) or an individualized hMG regimen, and laparoscopy was performed 36 hours after hCG administration. The length of the luteal phase was significantly longer (P less than 0.05) in the CC-treated group as compared with the hMG-treated group. The pattern of serum E2 levels differed significantly (P less than 0.01) in that E2 levels were lower in the early and midluteal phase in CC-stimulated cycles; in addition, a delayed second E2 peak was observed in the late luteal phase in these women. Serum P levels, however, were lower in the hMG-stimulated group. Analysis of FF hormone concentrations revealed significantly (P less than 0.05) higher concentrations of E2 and androsterone in the FF of hMG-treated patients. It is concluded that follicular development in CC-stimulated cycles differs markedly from that in hMG-stimulated cycles. These differences may reflect either an altered follicular maturational process or may represent a direct inhibitory effect of CC on follicular steroidogenesis.     

In vitro fertilization and embryo transfer: treatment-dependent versus -independent pregnancies

In order to determine the true incidence of treatment-dependent versus -independent pregnancy in an in vitro fertilization (IVF) program, 274 women who underwent 492 cycles of superovulation were studied. Overall, the treatment-dependent pregnancy rate was 15%. The treatment-independent pregnancy rate was 6.6%. When a subgroup of individuals with at least one patent fallopian tube was selected for analysis, the treatment-dependent and -independent pregnancy rates were 13.9% and 11.9%, respectively. While the mean observation interval following an attempt at IVF was 2 years, 83.3% of all treatment-independent pregnancies occurred within 6 months after a trial of IVF-ET (embryo transfer). Patient characteristics that predispose to treatment-independent pregnancy are discussed.     

Effect of clomiphene citrate on follicular and luteal phase luteinizing hormone concentrations in in vitro fertilization cycles stimulated with gonadotropins and gonadotropin-releasing hormone antagonist

OBJECTIVE: To investigate the effect that clomiphene citrate exerts on luteinizing hormone (LH) concentrations in gonadotropin/gonadotropin-releasing hormone (GnRH) antagonist cycles. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Two groups of patients undergoing in vitro fertilization (IVF) were compared. In group I, 20 patients were stimulated with clomiphene citrate (CC) in combination with gonadotropins and 0.25 mg of Cetrorelix (ASTA Medica AG; Frankfurt am Main, Germany) and in group II, 20 patients were stimulated with gonadotropins and 0.25 mg of Cetrorelix. INTERVENTION(S): Blood sampling was performed in the late follicular, periovulatory, early, mid, and late luteal phases. MAIN OUTCOME MEASURE(S): Luteinizing hormone (LH), estradiol, and progesterone. RESULT(S): LH levels were significantly higher in group I than in group II on all the days studied. Progesterone serum concentrations were significantly higher in group II in the early luteal phase, but not in the follicular or the middle and late luteal phases. CONCLUSION(S): LH concentrations are significantly higher in the follicular and luteal phases in cycles stimulated with CC, despite GnRH antagonist administration. This observation might have implications for the dose of GnRH antagonist needed to suppress LH in the follicular phase and questions the need for luteal-phase supplementation in cycles in which CC was used.     

卵巢低反应者应用自然周期方案体外受精-胚胎移植的价值

目的探讨自然周期方案行体外受精-胚胎移植(IVF-ET)在卵巢低反应患者的应用。方法对南京大学医学院附属鼓楼医院生殖医学中心2003年11月至2007年7月20例卵巢低反应患者采用自然周期方案进行IVF-ET的临床资料进行回顾性分析。结果20例患者共进行41个起始周期。其中11个周期取消,取消率为26.8%。30个取卵周期中27个周期获得卵子,取卵周期获卵率为90.0%。19个周期进行胚胎移植,起始周期移植胚胎率46.3%,取卵周期移植胚胎率63.3%。临床妊娠6例,其中5例已经分娩,1例流产。移植周期临床妊娠率为31.6%,移植周期分娩率为26.3%。结论自然周期方案行IVF-ET对于卵巢低反应患者是一种简单有效的治疗方法。     

Heterotopic pregnancy after in vitro fertilization and embryo transfer

We have presented a second case of heterotopic pregnancy after IVF-ET. The most likely cause is direct extrusion of embryos through the tubal ostia by the hydrostatic pressure associated with ET. The diagnosis of ectopic pregnancy must be suspected clinically and not ruled out on the sonographic demonstration of an intrauterine pregnancy. Early diagnosis is essential for the prevention of significant maternal morbidity and mortality after IVF-ET.     

Cervical pregnancy after in vitro fertilization and embryo transfer

A case of cervical pregnancy after in vitro fertilization and embryo transfer is described. This unusual pregnancy ended at 26 weeks' gestation after hysterotomy and delivery of an 830 gm boy. We suggest that the in vitro fertilization procedure is one of the possible risk factors of cervical pregnancy.     

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。     

Preovulatory serum estradiol-17 beta values and ultrasound scans in 17 pregnancies which followed in vitro fertilization and embryo transfer after treatment with clomiphene and hCG

17 patients whom we treated with clomiphene and hCG became pregnant after in vitro fertilization (IVF) and embryo transfer (ET). We now report on our experience with preovulatory estradiol 17 beta values and ultrasonography in determining the time of hCG administration in these patients. The mean estradiol value just before the hCG injection was 329 +/- 75 pg/ml/follicle. The mean follicle diameter on ultrasound was 23.4 +/- 1.5 mm on the same day. In four cases, we only used estradiol values and in one case only ultrasound for the timing of the hCG injection. Both methods of monitoring follicular growth are discussed.     

体外受精－胚胎移植术后子痫前期患者临床特点分析

目的探讨体外受精与胚胎移植(in vitro fertilization-embryo transfer, IVF-ET)术后单胎妊娠与子痫前期的关系及临床特点。 方法回顾性分析2012年6月至2018年12月郑州大学第一附属医院产科收治的通过IVF-ET受孕的单胎子痫前期患者58例(IVF-ET组),同期自然受孕的单胎子痫前期患者100例(自然受孕组)的临床资料。比较两组孕妇的临床特点和妊娠结局。 结果IVF-ET组患者的平均住院日(8.74±4.98) d较自然受孕组(7.26±3.07) d长,t＝－2.314,P<0.05;发病时间(28.6±5.63)周和诊断孕周(32.0±6.07)周均早于自然受孕组(28.6±5.63)周和(33.9±4.28)周,t＝4.02和2.04,P<0.05;IVF-ET组尿蛋白(＋＋＋)的发生率34.5%、胸腹水发生率48.3%、胎儿宫内生长受限发生率41.4%均高于自然受孕组20%,29%和26%,P<0.05。 结论IVF-ET术后单胎子痫前期患者以严重尿蛋白和胸腹水为主要临床症状,胎儿不良结局主要为胎儿宫内生长受限。     

A short luteal phase in cycles stimulated with clomiphene and human menopausal gonadotropin for in vitro fertilization

Of 70 cycles stimulated with clomiphene and human menopausal gonadotropin (hMG) for an in vitro fertilization-embryo transfer (IVF-ET) program, a short luteal phase of 11 days or less was found in 18. In this group the mean estradiol and progesterone levels were elevated in the early luteal phase. Despite the elevated initial values, progesterone levels fell rapidly at the mid luteal phase as a sign of premature luteolysis. The mean total amount of gonadotropin administered and the mean number of follicles punctured and of oocytes recovered did not show any significant difference between the groups of normal and short luteal phases. The present findings support the theory that hyperestrogenism in the early luteal phase may initiate the premature luteolysis observed in clomiphene-menopausal gonadotropin-stimulated cycles.