Early pregnancy wastage after gamete manipulation

The outcome of 1034 pregnancies in women who conceived after referral for infertility management in seven treatment groups is detailed. The mean early pregnancy wastage (before 20 weeks gestation) was 27% and ranged from 18% after AID (artificial insemination by donor semen) to 33% after IVF-ET (in-vitro fertilization and embryo transfer). These differences were not due to maternal age which was similar in all groups (means between 29.7 and 32.7 years). Excluding the AID group, there was a high rate of ectopic pregnancy which was significantly higher after GIFT (gamete intrafallopian transfer) and was only partly related to underlying tubal disease. Blighted ova was the main category of early pregnancy loss and was highest after AIH (artificial insemination by husband's semen). There was a higher rate of biochemical pregnancies after GIFT, PROST (pronuclear stage tubal transfer) and IVF-ET. Our findings confirm a high pregnancy wastage rate in subfertile women and highlight deficiencies in the sperm separation, gamete handling and IVF/embryo culture techniques.     

Early pregnancy wastage after gamete manipulation

Summary. The outcome of 1034 pregnancies in women who conceived after referral for infertility management in seven treatment groups is detailed. The mean early pregnancy wastage (before 20 weeks gestation) was 27% and ranged from 18% after AID (artificial insemination by donor semen) to 33% after IVF-ET (in-vitro fertilization and embryo transfer). These differences were not due to maternal age which was similar in all groups (means between 29.7 and 32.7 years). Excluding the AID group, there was a high rate of ectopic pregnancy which was significantly higher after GIFT (gamete intrafallopian transfer) and was only partly related to underlying tubal disease. Blighted ova was the main category of early pregnancy loss and was highest after AIH (artificial insemination by husband's semen). There was a higher rate of biochemical pregnancies after GIFT, PROST (pronuclear stage tubal transfer) and IVF-ET. Our findings confirm a high pregnancy wastage rate in subfertile women and highlight deficiencies in the sperm separation, gamete handling and IVF/embryo culture techniques.     

Zygote intrafallopian transfer as a treatment for nontubal infertility: a 2-year study

Zygote intrafallopian transfer (ZIFT) was used as a treatment for long-standing nontubal infertility for a 2-year period. The overall clinical pregnancy rate for 114 tubal transfers was 40.4% with a delivery/ongoing rate of 34.2%. Concurrent use of in vitro fertilization and embryo transfer (IVF-ET) for tubal factor infertility gave significantly lower clinical pregnancy and delivery/ongoing rates (21.1% and 15.8%, respectively). The use of gamete intrafallopian transfer (GIFT) for nontubal infertility yielded a 32% clinical pregnancy rate and a 26% delivery rate for 53 transfers. Zygote intrafallopian transfer resulted in an implantation rate per zygote of 17% overall compared with 8.1% per embryo for IVF-ET and 11.2% per oocyte for GIFT. The transfer of three zygotes per patient gave the same clinical pregnancy rate as the transfer of four while reducing the incidence of multiple gestation from 19% to 7.8% per transfer. No significant decline in the clinical pregnancy or delivery rate was seen with ZIFT in women aged 25 through 39.     

Pregnancies following pronuclear stage tubal transfer

Pronuclear stage tubal transfer (PROST) is a technique that involves in vitro fertilization (IVF) of oocytes, followed by the transfer of pronuclear oocytes into the fallopian tubes. It has been developed for its prognostic value of confirming fertilization in couples with oligospermia or asthenospermia and enabling fertilization in cases with antispermatozoal antibodies (ASAB). PROST has provided useful diagnostic information in the management of couples who have failed to conceive in other treatment programs and has particular advantages over IVF for those receiving fresh donated oocytes for ovarian failure. Fourteen pregnancies resulted from 52 transfers, providing a pregnancy rate of 27% per transfer. The pregnancy rates were higher than a matched IVF series in the male factor and female ASAB groups and reached statistical significance for the ovum donation group. It is anticipated that both pregnancy rates and fetal wastage will be improved over conventional IVF and embryo transfer for the described infertility groups.     

The influence of infertility etiology on the outcome of IVF-ET and GIFT treatments

The present report examines retrospectively the success rates of both in-vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) in relation to the underlying infertility disorder. Reduced fertilization rates were seen when the male partner was oligospermic or had both IgA and IgG in his semen, or the female partner had elevated LH concentrations during the follicular phase. In IVF-ET, the chance of pregnancy was reduced in women with elevated LH concentrations or endometriosis. Pregnancy rates for patients treated in the GIFT program were significantly better (P less than .001) than for those treated by IVF-ET. Of special interest was the finding of an improved chance of pregnancy for patients with severe endometriosis treated by GIFT (P less than .001). With oligospermia, pregnancies were only achieved in the GIFT program when the insemination number was increased. The pregnancy outcome was similar in both programs, with approximately 70% of pregnancies delivering beyond 20 weeks' gestation. However, there was a high rate of ectopic pregnancy, particularly in cases with underlying tubal disease. These findings have led to revised guidelines for the accurate counseling of patients, and provide further insight into the possible mechanism of various disorders contributing to infertility.     

An analysis of factors associated with ectopic pregnancy following in vitro fertilization and embryo transfer

Five ectopic pregnancies occurred in 75 in vitro fertilization and embryo transfer (IVF-ET) pregnancies (6.7%) in Ogikubo Hospital IVF program between 1985 and 1989. The indication for IVF in 70 pregnancies was a tubal factor. Thirty cases were among 70 pregnancies with hydrosalpinx, and 40 cases were with other tubal conditions. All of the five cases had tubal disease. Four of them had hydrosalpingos. The percentage of ectopic pregnancies for the 30 pregnancies with hydrosalpinx was 13.3%, while for 40 pregnancies with other tubal conditions it was 2.5%. However, there was no significant difference between the two groups. No correlation was found in other parameters including superovulatory methods, oocyte recovery procedure, number of embryos transferred, embryo transfer procedure, and endocrine changes after embryo transfer. In this study, we were unable to identify a difference between ectopic pregnancy and intra-uterine gestation in IVF-ET. However, further study is required to clarify whether hydrosalpinx increases the risk of ectopic pregnancy in IVF-ET.     

In vitro fertilization with concurrent pelvic reconstructive surgery

The recent advent of ultrasound-guided follicular aspiration by various approaches now allows access to ovaries previously deemed inaccessible by laparoscopy; however, a small group of candidates for in vitro fertilization and embryo transfer (IVF-ET) require laparotomy for associated gynecologic disorders. Twenty-five IVF-ET cycles at the time of laparotomy were compared with 309 IVF-ET cycles in which oocytes were retrieved laparoscopically. Five pregnancies occurred in the IVF-ET cycle with laparotomy and one pregnancy occurred spontaneously following microsurgical tubal reconstruction. The pregnancy rate per embryo transfer was 25% in the laparotomy IVF-ET patients compared with 15.4% for the laparoscopy IVF-ET group. Obvious advantages of combining IVF-ET and pelvic reconstructive surgery include a single anesthesia exposure and economic benefits. Patients with a long history of infertility undergoing tubal reconstructive surgery may be offered combined IVF-ET. Extended anesthesia exposure with pelvic surgery demonstrated no adverse effects on the pregnancy rate.     

Success of in vitro fertilization and embryo transfer in relation to the causes of infertility

In 1984 163 patients were treated in our in vitro fertilization program, including 4 patients accepting embryos from the oocyte and embryo donation program. Twenty pregnancies were achieved with an average chance per transfer of 16,6%. The final success of IVF strongly depends on the cause of infertility. The best results were obtained for patients with tubal infertility, with a pregnancy rate of 15% per laparoscopy and 19% per transfer. There is a significant decrease in oocyte cleavage rate from tubal (61%) to male infertility (13%). Once the barrier of embryo formation is taken, there is no marked difference in the mean number of embryos transferred on the pregnancy rate after transfer, among the different patient groups. In patients with tubal infertility the pregnancy rate per cycle remains constant, resulting in a cumulative pregnancy rate of 40% after 3 cycles.     

In vitro fertilization program. Preliminary results

Three infertile couples were submitted to in vitro fertilization and uterine embryo transfer (IVF+ET) and 7 to in vitro fertilization and pronuclear stage tubal transfer (IVF+PROST). In order to programmed menstruation Norethisterone, 10 mg daily, were administered during the cycle preceding the one of controlled ovarian hyperstimulation. In order to inhibit endogenous production of FSH and LH, leuprolide acetate, a Gn-RH agonist, was injected subcutaneously 1 mg daily during 6 days and 0.5 mg fowardly from the luteal phase of the cycle proceeding the one of hyperstimulation until the day of HCG administration. To achieve superovulation pure FSH (Metrodine), HMG (Pergonal) and HCG (Endocorion) were used. Oocyte retrieval was performed through transvaginal puncture under ultrasonographic control. For oocyte and embryo identification and classification, spermatozoa separation and capacitation and gamete insemination and incubation procedures habitual techniques were employed. Pronuclear embryo tubal transfer was performed through a laparoscope 17 hours after insemination and embryo transfer to the uterine cavity after 48 hours. Nine of 10 patients responded to gonadotrophin hyperstimulation and were submitted to ovarian puncture. 69 oocytes (7, per patient) were obtained, 59 (81.15% of which were mature. 74.55% of the inseminated oocytes fertilized. Two patients got pregnant: one, submitted to IVF+PROST, presently has a multiple pregnancy with triplets and the second, submitted to IVF+UT, had a missed abortion at 8 weeks of pregnancy.     

Simultaneous bilateral tubal pregnancies after in vitro fertilization and embryo transfer: report of a case.

Ectopic pregnancies continue to be a major complication of in vitro fertilization and embryo transfer (IVF-ET). A case of bilateral simultaneous tubal pregnancy after IVF-ET is described. The patient underwent ovum pick-up (OPU) through a laparotomy with concomitant pelvic surgery. Embryo transfer (ET) was performed two days after OPU; this resulted in bilateral tubal pregnancies, diagnosed and treated one month apart. There are several possible causal mechanisms for the increased rate of ectopic pregnancies following IVF-ET. It is important to recognize that care in the transfer technique, with respect to the catheter position and limiting the volume of transfer medium to 20 microL, and an awareness of previous occlusion of the tubal ostia, or of a salpingectomy before IVF-ET, can help to minimize this complication rate. Two important points are the possibility of a simultaneous bilateral tubal pregnancy after IVF-ET, and the necessity of carefully examining both adnexa at the time of surgery for an ectopic pregnancy. Early and accurate diagnosis of a simultaneous bilateral ectopic pregnancy can prevent the necessity of a second operation and reduce maternal morbidity and mortality.     

Efficacy of assisted reproductive technology during diagnostic and operative infertility laparoscopy

Women being evaluated for infertility were offered assisted reproductive technology at the time of diagnostic laparoscopy. Oocyte retrieval was performed after ovulation induction in 33 women, of whom 19 had concurrent operative laparoscopy. Gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF) and embryo transfer were performed subsequently depending on laparoscopic assessment of pelvic architecture, oocyte maturity, and semen parameters. The clinical pregnancy rate was 24% per cycle and 28% per gamete or embryo transfer (four pregnancies after GIFT and four after IVF/embryo transfer). The clinical pregnancy rate per transfer did not differ significantly between the 19 women who had therapeutic operations in conjunction with laparoscopy (lysis of adhesions and/or fulguration of endometriosis) and the 13 who did not (25 versus 30%; P greater than .05). Assisted reproductive technology can be performed successfully during diagnostic infertility laparoscopy. Operative endoscopic manipulation did not adversely influence pregnancy outcome.     

Gamete and zygote intrafallopian transfers and related techniques.

Until recently, most authors reported superior results (ie, higher implantation and pregnancy rates) with gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) compared with results using in vitro fertilization-embryo transfer (IVF-ET). According to these investigators, the advantages of tubal over uterine transfer are related mainly to a stable tubal environment and a more appropriate arrival time of the embryo into the uterine cavity. However, more recently, the use of IVF-ET has been increasingly extended to etiologies other than tubal infertility. Indeed, the recent simplification of this technique and the achievement of pregnancy rates comparable to those obtained with tubal transfers have seriously questioned the value of ZIFT and any other type of tubal embryo transfer. As discussed in this review, the results obtained with various transfer procedures in nontubal infertility must still prove ZIFT to be a more effective procedure than IVF-ET. Efforts to develop transcervical methods of transfer to the tube have not translated into higher pregnancy rates than those with IVF-ET. On the other hand, laboratory conditions appear to affect embryos in ways not corrected by the tubal milieu. Negative effects of laboratory conditions on embryos are confirmed by differences in results between GIFT and ZIFT that are accentuated with age. The results obtained with GIFT in patients 40 years of age and older seem to emphasize not only the high compliance of the endometrial receptivity but also the relevance of the biologic potential of the embryos in the process of implantation at this age.     

Tubal embryo transfer for the treatment of infertility.

The outcome of treatment for male factor infertility with either gamete intrafallopian transfer (GIFT) or in vitro fertilization and embryo transfer (IVF/ET) has been unsatisfactory. A better approach may be tubal embryo transfer (TET). In our medical center, from November 1989 to December 1990, 80 couples (male factor, n = 35, non-male factor, n = 45) entered our program for TET. Superovulation was conducted with either human menopausal gonadotropins (hMG) or gonadotropin-releasing hormone agonist (GnRH-a, buserelin)/hMG. Ovum retrieval (OR) was possible in 73 patients and successful fertilization after insemination occurred in 64 of them. TET was performed only when there was at least one grade III-V embryo. The mean number of embryos transferred was 3.92 +/- 0.13 (range 1-5). There were 35 pregnancies out of 55 TET (64% per TET, 48% per OR). In the group with male factor infertility, OR occurred in 32, and 24 achieved fertilization. Ten pregnancies were achieved after 19 TET (53% per TET, 31% per OR). In comparison, the group with non-male factor infertility had a higher pregnancy rate (69% per TET and 61% per OR). There have been 15 live births, 14 ongoing pregnancies (eight sets of twins and 21 singletons), five abortions and one ectopic pregnancy. Our results indicate that: 1) TET is a valuable treatment for non-tubal factor infertility; and 2) in the group with male factor infertility, it has the advantages of demonstrating fertilization in vitro and preventing unrewarding laparoscopies.     

混合抗球蛋白反应试验与体外受精-胚胎移植治疗关系的研究

目的:探讨混合抗球蛋白反应试验(MAR)与常规体外受精-胚胎移植(IVF-ET)治疗的关系。方法:回顾性分析562例第1次行IVF治疗不孕患者的临床资料,按照MAR检测结果将IVF周期分成4个区间组:<10%,10%~30%,30%~50%,>50%,分析各组间受精率、胚胎发育及临床妊娠情况。结果:540个IVF移植周期中共获得279例妊娠,周期妊娠率为51.7%。MAR>50%组的受精率显著低于其余各组(P<0.05),而各组间女方年龄、不孕年限、受精失败率、精子密度、精子活动率、正常形态精子百分率、优质胚胎率、胚胎种植率、临床妊娠率及流产率比较则均无统计学差异(P>0.05)。结论:MAR检测结果在预测IVF受精结局中有一定的价值,但与IVF治疗的临床妊娠结局无关。     

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.     

体外受精-胚胎移植周期第次对其妊娠的影响

目的 探讨体外受精－胚胎移植（IVF－ET）周期第次对其妊娠的影响。方法 回顾性分析妇性输卵管因素不孕行IVF－ET的908个周期的资料。结果 胺患者进行IVF－ET周期治疗的第1次、第2次、第3次、第4次及以上分4组，其种植率分别为17.6%、17.5%、8.7%、4.6%，经分别为41.1%、40.2%、21.1%、17.2%。进行IVF－ET周期第3次及以上的种植率肽临床妊娠率比周期第1次、第2次低，经x^2检验，有统计学意义（P＜0.001）。结论 随患者进行IVF－ET周期第次的增加，IVF－ET种植率及临床妊娠率逐渐下降，尤其是第3周期以上者更为明显。     

An analysis of factors associated with ectopic pregnancy in a human in vitro fertilization program

Between 1980 and 1985, in Monash University in vitro fertilization (IVF) program, ectopic pregnancy occurred in 10 of 256 IVF pregnancies. The incidence of ectopic pregnancy between 1983 and 1984 was 4% of the total pregnancies, or 4.2% of pregnancies excluding biochemical pregnancies. The incidence of ectopic pregnancy was distributed equally across the infertility classifications (tubal, idiopathic, male factor, and mixed). There appeared to be no relationship between superovulatory methods, endocrine changes before egg recovery, laparoscopic procedures, embryo transfer procedures, and number of embryos transferred. Nine of the ten patients were classified as having either tubal factor infertility before IVF or chronic tubal inflammation, which probably existed at the time of embryo replacement. No ectopic pregnancies were recorded in the 33 pregnancies obtained with superovulation with the use of clomiphene citrate alone. We were unable to identify a major predisposing factor for ectopic pregnancy in IVF.     

经阴道输卵管插管行配子输卵管移植的临床初步研究

目的 了解经阴道配子输卵管移植治疗非输卵管性不孕症（子宫内膜异位症、男性少弱精症、不明原因不孕等）的效果。方法 对２１例（２３个周期）不孕症患者分别采用（１）绝经期促性腺激素（ｈＭＧ）／ｈＣＧ（７个周期）;（２）卵泡刺激素（ＦＳＨ）／ｈＣＧ（２个周期）;（３）短方案促性腺激素释放激素激动剂（ＧｎＲＨ－ａ）／ｈＭＧ／ｈＣＧ（２个周期）;（４）长方案ＧｎＲＨ－ａ／ＦＳＨ／ｈＭＧ／ｈＣＧ（１２个周期）进     

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。     

Bilateral Ovarian Pregnancy After in Vitro Fertilization and Embryo Transfer in a Patient with Tubal Factor Infertility

Primary ovarian pregnancy is very rare event after natural pregnancy or assisted reproductive technology (ART) procedures. Although there are a few reports about unilateral ovarian pregnancy after in vitro fertilization and embryo transfer (IVF-ET), there has been no report about bilateral ovarian pregnancy. Moreover, it is difficult to diagnose an ovarian pregnancy following in vitro fertilization and embryo transfer because of enlarged ovary, fluid collection in pelvic cavity, and its low incidence. We present a case of a patient who underwent IVF-ET due to tubal factor infertility, but the patient developed bilateral ovarian pregnancy and was performed both ovarian wedge resection through laparotomy.