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.     

The relative chance of pregnancy following tubal or uterine transfer procedures

In a 7-month study period, a total of 113 pregnancies were generated in 380 women (30%) undergoing transfers in one of four assisted conception procedures: gamete intrafallopian transfer (GIFT), pronuclear stage tubal transfer (PROST), tubal embryo stage transfer (TEST), and in vitro fertilization and embryo transfer (IVF-ET). It was shown that both the pregnancy rate per transfer procedure and the number of pregnancy sacs arising per embryo transferred were significantly higher among the groups having tubal transfer (P less than 0.001). There were no significant differences in the pregnancy or implantation rates among the three groups having tubal transfer procedures when the GIFT results were adjusted for a 72% fertilization rate noted in the combined IVF-ET and PROST groups. Early pregnancy wastage showed a similar pattern among the four groups and, overall, 67% of pregnancies advanced beyond 20 weeks.     

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.     

Gamete intrafallopian transfer in the treatment of infertility: the first series at the University of Palermo

Twenty-six couples with unexplained infertility (UI), nine women with repeated failures of artificial insemination with donor semen (AID), three women with mild endometriosis, three with periadnexal adhesions, one with hostile (not immunologic) cervical mucus, and one couple in which the male partner was affected by asthenospermia were treated by the gamete intrafallopian transfer (GIFT) technique. Three different protocols for controlled ovarian hyperstimulation were used, and an adequate follicular growth and oocyte maturation were achieved in all cases. Seventeen pregnancies were obtained, for a global pregnancy rate of 38.6%. Two pregnancies (11.7%) ended in clinical abortions, and one (5.8%) was a tubal pregnancy. Of the ongoing pregnancies, one is twin and two are triplets. Seven pregnancies (six ongoing, one abortion) were obtained in the UI group (26%), six (all ongoing) in the failed AID group (66.6%), two continuing pregnancies in the three patients with endometriosis (66.6%); the tubal pregnancy and one clinical abortion occurred in the group with adnexal adhesions. No pregnancies were obtained in the patient with hostile cervical mucus and in the couple with infertility presumably due to poor semen. These encouraging results and the simplicity of the technique suggest that GIFT could be an effective approach that could be programmed during a well-timed laparoscopy where persistent infertility exists in association with apparently normal fallopian tubes.     

Successful treatment of failed AID cases by use of gamete intra-fallopian transfer using donor semen (GIFT (D)).

Over a 13-month period in a newly opened assisted conception unit at the Women's Hospital, Liverpool, gamete intra-fallopian transfer using donor semen, GIFT (D) was offered to eighteen couples who had failed to conceive after numerous cycles of treatment with artificial insemination by donor semen (AID). The indication for the use of donor semen was either azo- or severe oligoaesthenospermia, and, in addition, the female partners have been exhaustively investigated with no major cause found to account for the couple's infertility. Using a basic clomiphene citrate and human menopausal gonadotrophin protocol it was possible to achieve a pregnancy rate of 56% per GIFT (D) cycle. As a consequence of these results it is now our policy to treat couples whose infertility is due to an unresolvable male factor with AID for 12 cycles only. If they have been unsuccessful in achieving a pregnancy after this time, they are offered GIFT (D).     

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.     

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.     

Successful gamete intrafallopian transfer following failed artificial insemination by donor: evidence for a defect in gamete transport?

Gamete intrafallopian transfer (GIFT) was offered as an alternative treatment to 48 women who failed to conceive after artificial insemination with donor semen (AID) in numerous attempts (9 to 24 cycles). The evaluation of these women showed no major cause of infertility as evidenced by normal endocrine, cervical, uterine, and tubal factor studies. Their partners were either azoospermic or severely oligoasthenospermic. During the GIFT cycle, follicular development was induced with (1) clomiphene citrate (days 3 to 7) plus human menopausal gonadotropins (hMG) from day 6 on or (2) human follicle-stimulating hormone (days 3 to 4) plus hMG (day 5 on), until ultrasound revealed 2 follicles 16 mm and serum estradiol (E2) was greater than 700 pg/ml. Human chorionic gonadotropin (hCG) 10,000 IU was administered, and 36 hours later follicular aspiration was performed. One to three oocytes and 100,000 motile sperm were transferred to each fallopian tube through the fimbria via laparoscopy or minilaparotomy. Twenty-seven clinical pregnancies were achieved (56%) per GIFT cycle. Eight miscarriages occurred during the first trimester (29% of all pregnancies), whereas no ectopic pregnancies were observed. These data conclusively show the value of the GIFT procedure in the treatment of cases with failed AID.     

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.     

Treatment-independent, treatment-associated, and pregnancies after additional therapy in a program of in vitro fertilization and embryo transfer

Although the technique of in vitro fertilization and embryo transfer (IVF-ET) was developed for couples with untreatable tubal factor infertility, IVF-ET is now being applied to women with other causes of infertility and normal pelvic anatomy. In an effort to determine the treatment-independent pregnancy rate, we retrospectively reviewed the first 245 couples enrolled in the IVF-ET program at Duke University Medical Center. There were 19 treatment-independent pregnancies in 18 women and 3 treatment-associated pregnancies in cycles in which the oocyte retrieval was canceled (in 2 women washed intrauterine insemination was substituted for oocyte retrieval). Six pregnancies were established after an unsuccessful attempt at IVF-ET with additional non-IVF-ET therapy, including washed intrauterine insemination in three couples, and donor insemination in two couples. These observations suggest that a significant number of treatment-independent pregnancies will occur in couples clinically deemed appropriate for IVF-ET, pregnancies can be established in cycles of controlled hyperstimulation without oocyte retrieval, and additional non-IVF-ET therapy can result in pregnancy despite failure of IVF-ET in selected couples.     

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.     

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.     

Treatment of patients with unexplained infertility: gamete intrafallopian transfer (GIFT) versus tubal embryo transfer (TET).

This study compares the results of 65 cycles of gamete intrafallopian transfer (GIFT), and 19 cycles of tubal embryo transfer (TET) in couples with unexplained infertility (UI). Oocyte retrievals were carried out by laparoscopy in GIFT and transvaginally in TET, in which the embryos were transferred by laparoscopy into the fallopian tubes 48 hours later. The mean age, duration of infertility, serum estradiol levels on the day of human chorionic gonadotropin administration, number of large follicles (mean diameter greater than 10 mm) and the number of oocytes recovered were similar between these two groups. From the 65 GIFT cycles, 20 clinical pregnancies resulted (30.8%). From the 19 cycles of TET, 10 conceptions occurred (52.6%). The implantation and pregnancy rates after TET were higher than that after GIFT, but the differences were not statistically significant. The data suggest that GIFT has a similar success rate to TET in couples with UI.     

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.     

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     

Early experience with in vitro fertilization-embryo transfer and gamete intrafallopian transfer in a Nigerian hospital

We present our early experience with in vitro fertilisation-embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) in a Nigerian Hospital. Twenty-one patients were recruited, 11 patients for the IVF-ET program and 10 for the GIFT program. In the IVF program the oocyte recovery rate was 100%, the fertilization rate was 66% and the cleavage rate was 97% but no live pregnancies were achieved. In contrast, one live delivery was achieved with GIFT. These results suggest that both IVT-ET and GIFT are feasible in developing countries.     

Gamete intrafallopian transfer by hysteroscopy as an alternative treatment for infertility

OBJECTIVE: To evaluate efficacy and safety of the hysteroscopic cannulation by flexible catheter of the fallopian tubes for gamete intrafallopian transfer (GIFT). DESIGN: We studied the pregnancy rate (PR) and the safety of this new technique. SETTING: All patients were enlisted for GIFT at our Reproductive Medicine Unit. PATIENTS: We treated 26 patients whose infertility causes were terminal tubal damage, male factors, unexplained factors, and endometriosis. Patients with uterine tubal ostia unsuitable for gamete transfer or cervical incontinence were not included in the group. INTERVENTIONS: The patients underwent ovulation induction and oocyte retrieval by transvaginal ultrasonically guided puncture. The gamete transfers were carried out by hysteroscopic procedure using a flexible catheter put through the operating channel. MAIN OUTCOME MEASURE: The efficacy was evaluated by the PR (25.9%). RESULTS: Seven clinical pregnancies were obtained, but two patients aborted during the first weeks of pregnancy. No ectopic pregnancies were observed. CONCLUSIONS: Our results indicate that hysteroscopic GIFT is an alternative, safe, effective, and not invasive technique for fertility problems.     

Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age

To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older. One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40. Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.     

Very early pregnancy wastage in in vitro fertilization and embryo transfer (IVF-ET)

The occurrence and incidence of early pregnancy wastage in an in vitro fertilization and embryo transfer (IVF-ET) program have been studied in 750 patients. In 297 (39.6%) a pregnancy was diagnosed; of these, 14.8% were biochemical and 24.8%, clinical pregnancies. In the latter group 23.6% aborted, while 75.8% had clinical ongoing pregnancies. The mean embryo quality score of the biochemical pregnancy group was similar to that of the clinical ongoing pregnancy group but statistically different from that of the clinical abortion group (P<0.005). Furthermore, the clinical ongoing pregnancy rate in women with previous biochemical pregnancy was 24.7%, a significantly higher percentage compared to clinical ongoing pregnancies achieved in IVF-ET cycles (P<0.05). It is possible that biochemical pregnancy does not represent an index for infertility but rather an intact stage of reproduction leading toward implantation. The high clinical pregnancy rate in subsequent cycles may probably serve as an encouraging sign or a marker for future clinical 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.