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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).

Adult↗

Ovulation induction with gonadotropins and intrauterine insemination compared with in vitro fertilization and no therapy: a prospective, nonrandomized, cohort study and meta-analysis.

OBJECTIVES: To determine whether one to four cycles of ovulation induction with hMG and IUI or one cycle of IVF results in the highest pregnancy rate and is least expensive and whether published pregnancy rates for one to four cycles of hMG and IUI results in a higher pregnancy rate than rates for one cycle of IVF, zygote intrafallopian transfer (ZIFT), or GIFT. DESIGN: Prospective, nonrandomized, cohort study. Patients were excluded who were infertile for < 18 months, had a significant male factor, had greater than mild endometriosis, or had bilateral nonpatency of the fallopian tubes. Cohort groups included 47 hMG and IUI patients (99 cycles), 19 IVF patients (19 cycles), and 21 patients (210 cycles) receiving no treatment. A meta-analysis on accumulated hMG and IUI data using similar entry criteria was also performed. Theoretical calculations were performed and stable fecundity assumed to compare with national data on IVF, ZIFT, and GIFT. SETTING: Fertility Center, Division of Reproductive Endocrinology, University of Utah, Salt Lake City, Utah. RESULTS: A course of therapy with one to four cycles of hMG and IUI was just as effective as one cycle of IVF in achieving pregnancy. No significant difference in pregnancy rates was found between one IVF cycle and one to four cycles of hMG and IUI in our population. In vitro fertilization was more expensive than four cycles of hMG and IUI. Both IVF and hMG and IUI were more effective than no therapy. Published data also suggest that four cycles of hMG and IUI theoretically result in higher pregnancy rates than one cycle of IVF, ZIFT, or GIFT. CONCLUSION: Cost-benefit analysis comparing hMG and IUI, IVF, and no therapy in infertility patients may favor a course of four cycles of hMG and IUI as the first line of therapy. Using meta-analysis and theoretical assumptions, the pregnancy rate for one cycle of hMG and IUI is inferior to IVF, GIFT, or ZIFT; two cycles are comparable to IVF or ZIFT and inferior to GIFT; three cycles are superior to IVF or ZIFT and comparable to GIFT; and four cycles are theoretically superior to all techniques.

Adult↗

Luteal function associated with single, multiple and ectopic embryo implantation in natural cycles or after ovarian hyperstimulation for in-vitro fertilization/gamete intra-fallopian transfer.

Levels of reproductive steroids and gonadotrophins were analysed retrospectively during the peri-implantation period following non-conceptional and conceptional natural cycles and in cycles associated with ovarian hyperstimulation for in-vitro fertilization or gamete intra-Fallopian transfer. In cycles not associated with conception, the luteal phase of hyperstimulated cycles (n = 100) was characterized by higher serum progesterone and oestradiol levels (P less than 0.01) and with an earlier decline in steroids than in natural cycles (n = 21). On day 11 (day of oocyte recovery = day 0), the level of progesterone in twin (n = 59) and triplet (n = 13) pregnancies was higher than singleton pregnancies (n = 176) (P less than 0.006, P less than 0.006 respectively) while those destined to abort (n = 66) had lower progesterone levels (P less than 0.01). Ectopic implantation (n = 11) had the lowest progesterone concentrations on day 11 (P less than 0.01) and this may imply a delay in corpus luteum rescue or a later implantation time than intrauterine conception.

Clomiphene↗

Fertilization in vitro of supernumerary oocytes following gamete intra-fallopian transfer (GIFT).

Gamete intra-Fallopian transfer (GIFT) was performed in 130 treatment cycles over a 17-month period. In 91% (118/130) of the cycles one or more oocytes were available for insemination in vitro and only GIFT cycles with supernumerary oocytes were included in the present study. Pituitary and ovarian suppression was achieved with buserelin followed by stimulation of multifollicular development by human menopausal gonadotrophin (HMG). Failure of supernumerary oocytes to fertilize was associated with a significantly reduced pregnancy rate (3/23; 13%) compared to cycles where fertilization occurred in vitro (35/95; 37%). These findings demonstrate that the outcome of IVF of supernumerary oocytes may be of particular diagnostic value in couples where the female partner has not conceived following treatment by GIFT after pituitary down-regulation with buserelin and ovarian stimulation with HMG.

Adult↗

A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement.

A luteal phase defect has been demonstrated in cycles stimulated using a protocol including a gonadotrophin releasing hormone agonist (GnRHa). We have conducted a randomized prospective study of luteal and early pregnancy supplementation in 262 women selected for in-vitro fertilization (IVF), gamete intra-Fallopian transfer (GIFT) or zygote intra-Fallopian transfer (ZIFT). Either intramuscular progesterone in oil (50 mg/day) or intravaginal micronized progesterone (600 mg/day) was used as luteal supplement. In association with oestradiol valerate, progesterone administration was initiated from the day before oocyte retrieval until the 12th week of pregnancy. The implantation rate just failed to reach statistical significance (P = 0.07) in favour of the group receiving intravaginal progesterone. In the latter group, we observed a higher clinical pregnancy rate (33.6 versus 26.7%, not significant). Despite lower plasma progesterone levels, a lower first trimester abortion rate (P less than 0.05) was found in the intravaginally treated group. Intravaginal micronized progesterone was well tolerated by all patients and appeared more effective than intramuscular progesterone in improving the implantation rate, and in decreasing the incidence of abortions in stimulated cycles including GnRHa.

Administration, Intravaginal↗

A program of oocyte donation and gamete intra-fallopian transfer.

The outcome of a series of 19 patients with premature ovarian failure (POF) undergoing gamete intra-Fallopian transfer (GIFT), utilizing donated oocytes, is described. The steroid replacement protocol consisted of the administration of increasing dosages of 17 beta-oestradiol (E2) and progesterone (P4). Hormonal replacement was maintained until day 100 of gestation. All patients underwent an evaluation cycle in which serum levels of E2 and P4 were monitored and an endometrial biopsy was performed either 7 or 11 days after initiation of progesterone administration. All cases of GIFT were performed between days 12 and 15 of the induced menstrual cycle. Of the 19 patients treated, 11 became pregnant, giving a clinical pregnancy rate of 58% (visualization of gestational sac by ultrasound). Two patients aborted between the 4th and 5th weeks of gestation. No ectopic pregnancies occurred. Three of the seven deliveries involved multiple births. Details of the circulating hormone levels and endometrial response are discussed.

Adult↗

Post-operative artificial insemination--does it improve GIFT outcome?

Based on a retrospective study of our gamete intra-Fallopian transfer (GIFT) programme we have analysed 102 cycles where a standard GIFT procedure was implemented and 92 cycles where a post-operative intrauterine and intracervical insemination (post-operative IUI/ICI) was performed, in addition to GIFT. Our comparison suggests that the pregnancy outcome has been significantly improved (P less than 0.05) by this additional post-operative IUI/ICI. The standard GIFT group (102 cycles) yielded 38 clinical pregnancies and, ultimately, 29 delivered pregnancies (37.2/28.4%), whilst the post-operative IUI/ICI group (92 cycles) gave 48 clinical pregnancies initially and, currently, 38 pregnancies are ongoing or delivered (52.2/41.3%). The possible implications of the 'normal' presence of spermatozoa in the human female tract as an explanation for this improvement is discussed, and the adoption of IUI/ICI after GIFT is proposed, following a prospective controlled study.

Abortion, Spontaneous↗

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Adult↗

Induction of multiple follicular development for IVF.

It is now accepted, almost universally, that multiple follicular development is a pre-requisite for a successful assisted conception programme. The reasons for this are based on abundant clinical evidence from the major IVF and GIFT centres of the world indicating the benefits of having multiple gametes available for transfer. The more embryos transferred, the better the pregnancy rate; the more embryos available for cryopreservation the better the chances of subsequent survival and replacement. However, the vast majority of patients in IVF/GIFT programmes have normal ovarian and pituitary function designed to produce a single dominant follicle and oocyte each month. Obtaining multiple follicular growth requires pharmacological manipulation of ovarian function and complicating factors may arise from both ovarian and pituitary sources. Methods employed to achieve multiple follicular growth vary considerably in the different centres and experiments continue in attempts to find either the simplest or the perfect system, or both. This would provide abundant oocytes and the ideal hormone environment for implantation, with no interfering factors at either the ovarian or endometrial level, while avoiding the drawbacks commonly encountered such as pre-operative ovulation or hyperstimulation syndrome. It should also be inexpensive, although in reality cost-effectiveness is more important.

Female↗

The use of gamete intra-fallopian transfer with donor spermatozoa after failed donor insemination.

The objective of this study was to assess the efficacy of gamete intra-Fallopian transfer (GIFT) in couples who had failed to conceive by donor insemination. The study was designed as a retrospective analysis of couples who entered the GIFT programme after 12 failed cycles of donor insemination. It took place in a comprehensive reproductive clinic with large donor insemination and in-vitro fertilization/GIFT programmes. A total of 197 patients received a total of 350 treatments from 1985 until 1992. Couples entered the GIFT programme with the routine stimulation and monitoring. The only difference was that frozen spermatozoa were used for the insemination. The main outcome measure was pregnancy, defined as a positive beta-human chorionic gonadotrophin (> 30 IU/l) at 16 days after replacement of gametes. The overall pregnancy rate achieved was 31% per cycle. Life table analysis showed a cumulative pregnancy rate of 75.4 +/- 5.7% after four cycles and 96.0 +/- 2.7% after eight cycles. It was concluded that the use of GIFT with donor spermatozoa is a highly effective treatment and should be offered to all couples who fail to conceive with donor insemination.

Cryopreservation↗

Measurement of noradrenaline, dopamine and serotonin contents in follicular fluid of human graafian follicles after superovulation treatment.

We measured the noradrenaline (NA), serotonin (5-HT) and dopamine (DA) contents of 47 normally maturated and 16 cystically degenerated follicular fluid samples obtained from patients involved in the in vitro fertilization and gamete transfer program. The patients were given human menopausal gonadotropin (HMG), as a superovulation treatment, and 7,500 IU human chorionic gonadotropin (HCG) to induce ovulation 34-36 h prior to the follicular puncture done by laparoscope. The NA content of the normally developed follicles was 11.4 + 8.4 micrograms/100 ml on average. For cystically degenerated follicles, the following data were obtained: 1.1 + 0.7 micrograms/100 ml (p less than 0.001). 5-HT and DA contents in the preovulatory follicles are 14.3 +/- 8.9 and 19.3 +/- 8.2 micrograms/100 ml, respectively; at the same time, 5-HT and DA contents in the cystically degenerated follicles were 12.2 +/- 6.2 and 12.7 +/- 6.8 micrograms/100 ml, respectively. They suggest that the higher amount of NA in the follicular fluid might play an important role in the mechanism of ovulation, the regulation of postovulatory tubal motility and the release of progesterone from granulosa cells.

Dopamine↗

[Analysis of noradrenaline, dopamine and serotonin levels in follicular fluid following superovulatory treatment].

The authors measured the noradrenaline (NA), serotonin (5-HT) and dopamine (DA) content of 47 normally maturated and 16 cystically degenerated follicular fluid samples obtained from patients involved in the in vitro fertilisation and gamete transfer program. The patients were given human menopausal gonadotropin (HMG) as a superovulation treatment, and they were given 7500 IE human Chorionic Gonadotropin (HCG) to induce ovulation 34-36 hours prior to the follicular puncture done by laparoscope. The NA content of the normally developed preovular follicles is 11.4 +/- 8.4 micrograms/100 ml on average. For the cystically degenerated follicles the data are following: 1.1 +/- 0.7 micrograms/100 ml (p less than 0.001). 5--HT and DA for the preovulatory follicles are 14.3 +/- 8.9 micrograms/100 ml and 19.3 +/- 8.2 micrograms/100 ml respectively; at the same time for the cystically degenerated follicles they are 12.2 +/- 6.2 micrograms/100 ml, and 12.7 +/- 6.8 micrograms/100 ml respectively. They presume that the higher amount of NA in the follicular fluid might play an important role in the mechanisms of ovulation, the regulation of postovulatory tubal motility, and the release of progesterone from granulosa cells.

Adolescent↗

GIFT or IVF for patients with patent fallopian tubes?

The pregnancy rate in a group of 39 couples who underwent in vitro fertilization (IVF) with donor sperm was compared with that of couples undergoing gamete intra-Fallopian transfer (GIFT) over the same period (31 December 1986 to 30 June 1991). The diagnostic status of the female partners in each group was qualitatively similar. The women had patent Fallopian tubes, mild endometriosis or minor tubal adhesions. The male partners in the GIFT group had normal or marginally abnormal semen parameters which were considered to be comparable to the post-thaw quality of the semen used in donor insemination (DI). The mean age of the women in the DI group was 32 years (range 25-40) which was similar to that in the GIFT group [32 years (24-39)]. The women in the IVF group had undergone a mean of eight cycles of DI before proceeding to treatment with IVF. There was no difference between the pregnancy rate in the two groups (log-rank test). These observations advance the proposition that IVF should be reconsidered as an effective treatment for women with patent Fallopian tubes.

Adult↗

Conscious sedation versus general anaesthesia for minilaparoscopic gamete intra-Fallopian transfer: a prospective randomized study.

BACKGROUND: Gamete intra-Fallopian transfer (GIFT) is a successful technique for infertile women, and is performed almost exclusively by laparoscopy under general anaesthesia. METHODS: We performed a prospective randomized study of 67 infertile patients to assess the efficacy of minilaparoscopic GIFT under conscious sedation/local anaesthesia (group A) compared with general anaesthesia (group B). Operative and discharge times and pregnancy outcome were evaluated in both groups. RESULTS: Operative time was similar in both groups. The rate of patients discharged 2 h after surgery was significantly higher in group A. The necessity for postoperative analgesics was significantly higher in group B. No significant differences were noted between the two study groups in terms of pregnancy outcome. CONCLUSIONS: Conscious sedation and local anaesthesia will allow us to perform an outpatient minilaparoscopic GIFT without the need for general anaesthesia. The simplicity of the method, and the quicker discharge time in comparison with general anaesthesia, offer a detectable benefit for patients.

Adult↗

Ultrasound evidence for variability in the size and development of normal human embryos before the tenth post-insemination week after assisted reproductive technologies.

Differences in human chorionic gonadotrophin (HCG), average chorionic sac diameter, embryo/fetus crown-rump length and biparietal diameter were determined in 107 singleton pregnancies delivered after 34 weeks, whose post-insemination age was precisely known as a result of in-vitro fertilization (n = 28) or gamete intra-Fallopian transfer (n = 79). Crown-rump lengths were interpreted in relation to the developmental stage of the embryo. A 7-fold to 10-fold difference in HCG levels was observed on post-insemination days 13-16. A 2-fold to 3-fold difference occurred in average chorionic sac diameter on days 25-36. A 2-fold difference occurred in crown-rump length on seven of 10 days prior to day 44. Biparietal diameter differed by no more than 42% from day 57-68 and 20% after day 68. Chorionic sac diameter, crown-rump length, and biparietal diameter were also related to newborn weight. The results suggest firstly that marked differences occur in the rate of early human development, secondly, that the differences occur prior to day 27 when observable cardiac activity begins, and thirdly, that the differences are minimized after day 68 when the embryonic period of development is completed.

Anthropometry↗

The concerns during assisted reproductive technologies (CART) scale and pregnancy outcomes.

OBJECTIVE: To determine whether concerns specific to IVF/GIFT (i.e., side effects, surgery, anesthesia, not enough information, pain, recovery, finances, missing work, and live birth delivery) that were measured by the previously validated Concerns During Assisted Reproductive Technologies (CART) instrument are negatively associated with reproductive endpoints. DESIGN: Prospective study. SETTING: Seven centers in Southern California between July 1993 and June 1998. PATIENT(S): One hundred fifty-one women completed two questionnaires at baseline and at the time of the procedure. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes aspirated and fertilized, number of embryos transferred, pregnancy rates, and live birth delivery rates. RESULT(S): At baseline, women who were concerned about the medical aspects (i.e., side effects, surgery, anesthesia, not enough information, pain, and recovery) of the procedure had 20% fewer oocytes retrieved and 19% fewer oocytes fertilized, while simultaneously adjusting for female age, race, education, smoking status, parity, type of assisted reproductive technologies (ART) procedure (IVF or GIFT), type of infertility, and number of previous attempts. Women who were very concerned about missing work had 30% fewer ooyctes fertilized. For women who were moderately concerned about missing work, the odds ratio was 2.83 for not achieving a pregnancy. Women who were extremely concerned about the finances associated with the procedure had a very high risk (odds ratio [OR] = 11.62) of not achieving a successful live birth delivery. CONCLUSION(S): The CART scale identified two areas of concerns for women undergoing IVF or GIFT: "missing work/finances" and "medical aspects of the procedure."

Absenteeism↗

Transvaginal crown-rump length measurements of 224 successful pregnancies which resulted from gamete intra-Fallopian transfer or in-vitro fertilization.

The crown-rump lengths (CRL) of 224 pregnancies which resulted from gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF) were assessed two to four times in the first trimester. The results were compared with some of the published articles which assessed CRL in spontaneous and induced pregnancies. The range of CRL measurements from this study was generally smaller than the previously published data, although all women went on to deliver normal fetuses at full term weighing > 2.5 kg. It was not possible to identify a clear reason for this finding, but factors which might have been relevant included population differences, more accurate estimation of ovulation/conception time, the exclusive use of vaginal ultrasonography in this study and variations in the embryonic implantation/development times. There is a need to review the commonly used CRL charts in view of the increasing use of transvaginal ultrasonography and the increasing number of pregnancies with known ovulation/conception times. Each centre should aim to establish the normal CRL range for its own population.

Adult↗

Influence of spermatozoa characteristics on gamete intra-fallopian transfer procedures: analysis of results obtained utilizing normozoospermic, oligoasthenozoospermic and donor spermatozoa.

The objective of this study was to analyze the efficacy of the gamete intra-Fallopian transfer (GIFT) procedure in relation to spermatozoa characteristics. A total of 268 infertile couples enlisted for GIFT were categorized into three groups on the basis of semen characteristics in the husband. These included oligoasthenozoospermic men in 88 retrieval cycles (group 1), normozoospermic men in 116 cycles (group 2) and azoospermic partners who needed donor semen in 86 cycles (group 3). All female patients had ovarian stimulation and laparoscopic GIFT. Pregnancy rates were significantly higher with donor spermatozoa than with oligoasthenozoospermic or normozoospermic spermatozoa, i.e. 51.1% versus 15.9% (P < 0.001), and 32.7% (P < 0.005). Implantation rates were significantly higher with donor spermatozoa than with normo- or oligoasthenozoospermic spermatozoa (P < 0.01). These data suggest that GIFT does not give good results with male factor infertility. Donor cryopreserved semen gives higher pregnancy and implantation rates than normozoospermic semen, and GIFT with donor spermatozoa gives a good chance of pregnancy to couples previously treated with artificial insemination using donor semen.

Female↗