Differences in the luteal phases after failed or successful in vitro fertilization and embryo replacement

Luteal phases after in vitro fertilization (IVF) and embryo replacement have been studied in 241 cycles. A positive correlation was observed between the follicular estradiol (E₂) peak and the progesterone (P) level on day 3 of the luteal phase, but not correlation was found between the E₂-peak value and the luteal-phase duration or midluteal P concentration. When the trials were classified in relation to their outcome (i.e., clinical pregnancies, chemical pregnancies, or failures), the mean P level on day 3 of the luteal phase was significantly higher in clinical pregnancies than in chemical pregnancies and in failures. Mean E₂ levels on day 3 were not significantly different among the three groups. Values of the E₂/P ratio were significantly higher in chemical pregnancies than in the other groups. No significant differences were observed among the three groups on day 8. When comparing trials ending in failure to those leading to clinical pregnancy for the same patients, pregnancies were obtained in cycles in which early luteal P was higher and the early luteal E₂/P ratio was lower than in failures cycles. These data suggest that high P levels and a low E₂/P ratio in the early luteal phase might have a favorable influence on the implantation process in human IVF.     

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.     

Microdose follicular phase gonadotropin-releasing hormone agonists (GnRH-a) compared with luteal phase GnRH-a for ovarian stimulation at in vitro fertilization

Objective: To compare an ovarian stimulation protocol using microdose follicular phase GnRH agonist (GnRH-a) and oral contraceptive (OC) pills to a luteal phase GnRH-a protocol.

Design: Retrospective analysis.

Setting: University affiliated IVF program.

Patient(s): One hundred seventy patients who underwent IVF and ET in 1996.

Intervention(s): Patients were assigned to either a midluteal start of leuprolide acetate (LA) 1 mg/d, reduced to 0.5 mg/d after addition of gonadotropins (LUT), or OC pills until cycle day 0 followed by 20 μg of LA every 12 hours on cycle day 3 with addition of gonadotropins on cycle day 5 (MICRO).

Main Outcome Measure(s): Number of FSH ampules, days of stimulation, peak E₂, and number of oocytes retrieved.

Result(s): There were no statistically significant differences in the main outcome measures between the two groups using an age-matched ANOVA. Clinical pregnancy rate per cycle start was not statistically different (LUT = 54%, and MICRO = 37%). The cancellation rate was significantly higher in the MICRO group (22.5% vs. 8.2%).

Conclusion(s): Given the higher cancellation rate in the microdose group, a randomized clinical trial is required to determine the possible benefit of a lower dose of GnRH-a in patients with normal ovarian function.     

Toxicity testing for human in vitro fertilization programs

Using a mouse embryo culture system, several procedures and materials associated with human in vitro fertilization protocols were tested for potential toxicity. Also, quality-control assays were performed for media prepared by nine different human in vitro fertilization programs. Detrimental effects upon embryo development were observed when culture media were exposed to the following substances: surgical instruments sterilized with Cidex or Cidex-7 or sterilized with ethylene oxide after packaging in Nest Protector Packs, various brands of surgical gloves, and various synthetic materials being evaluated as possible needle or catheter liners. Results from comparative testing of media and serum supplements prepared by different in vitro programs indicated a wide range in culture medium quality, as assayed by the ability of the reagents to support mouse embryo development. The importance of an animal model system available to all human in vitro programs for routine quality-control analysis and testing of novel uses of materials and innovative methods is discussed.     

Comparison of the efficacy and safety of two formulations of micronized progesterone (Ellios and Utrogestan) used as luteal phase support after in vitro fertilization

OBJECTIVE: To compare the efficacy and the tolerability of two different vaginal formulations of micronized progesterone, Ellios and Utrogestan, used for luteal phase support after an in vitro fertilization (IVF) cycle. DESIGN: Cohort study. SETTING: Fertility center in a university hospital. PATIENT(S(: One hundred twenty-three women who underwent IVF/intracytoplasmic sperm injection (ICSI) stimulated cycles from October 1998 to March 2000, who had at least six follicles of > or =14 mm on the day of hCG administration. INTERVENTION(S): Patients received Ellios pessaries (2 times 200-mg pessary/day) or Utrogestan capsules (2 x 100-mg capsules, two times a day). Progesterone was administered from the day of oocyte pickup (day 0) until menses or up to 10 weeks in pregnant patients. MAIN OUTCOME MEASURE(S): Progesterone levels, pregnancy rate, and tolerability tested by patient questionnaire. RESULT(S): The progesterone levels on days 0, 9, 16 were not statistically different between the two formulations. The pregnancy rate were similar in groups 1 and 2 (25.5% vs. 18.6%), whereas tolerance was significantly better in group 1 versus group 2 (vaginal discharge: 43% vs. 82%). CONCLUSION(S): The efficacy of the two formulations of progesterone is comparable, although the patient tolerance for Ellios is better.     

Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial

Objective: To evaluate the effect of intravenous immunoglobulin (IVIG) on pregnancy outcome in couples with repeated unexplained in vitro fertilization (IVF) failure.

Design: Prospective, randomized, double blind, placebo-controlled clinical trial.

Setting: A university-based and a free-standing IVF program.

Patient(s): Fifty-one couples with a history of repeated unexplained IVF failure who were preparing for another fresh IVF cycle or replacement of cryopreserved embryos.

Intervention(s): Eligible women underwent a standard IVF stimulation using a long luteal phase GnRH analog protocol. Cryopreserved embryos were replaced after endometrial preparation with oral micronized estradiol and subsequent vaginal progesterone. The women were randomly selected to receive IVIG (500 mg/kg) or an equivalent volume of normal saline. The first infusion was given on the day of embryo transfer or during the preceding 72 hours. The second infusion was given 4 weeks later if a clinical pregnancy was confirmed by ultrasound.

Main Outcome Measure(s): Live-birth rates.

Result(s): Overall, the live-birth rates were 4/26 (15%) for the IVIG group and 3/25 (12%) for the placebo group (P=0.52). There were 39 fresh IVF cycles, which yielded a clinical pregnancy rate of 28%, with live-birth rates of 4/21 (19%) for the IVIG group and 3/18 (17%) for the placebo group (P=0.59).

Conclusion(s): In this randomized clinical trial, IVIG did not improve the live-birth rate in couples with repeated unexplained IVF failure, stringently defined by known determinants of IVF outcome.     

Human amniotic fluid for fertilization and culture of human embryos: Results of clinical trials in human in vitro fertilization (IVF) programs

We report the outcome of clinical trials carried out in two IVF programs, comparing the use of human amniotic fluid (HAF) as a complete medium to Whittingham's T6 medium containing human serum T6+10% HS) for egg incubation, insemination, embryo culture, and embryo transfer. There were no significant differences in the clinical trials between HAF used alone as a complete medium and T6+10% HS in fertilization rates of eggs, cleavage rates of embryos up to 48 hours in culture, pregnancy success rates after embryo replacement or the outcome of pregnancies. There was no advantage in using T6+10% HS for fertilization of eggs and HAF as a complete medium for embryo culture and transfer in any of the parameters examined. We conclude that HAF does not meet the complete requirements of human eggs and embryos in vitro and further developments of culture media are required to obtain embryo development equivalent to that in vivo.     

Hysteroscopy in a program of in vitro fertilization

Two hundred twenty-four women underwent hysteroscopic evaluation without anesthesia after at least two failed attempts of in vitro fertilization and embryo transfer. One hundred fifty-three (68%) women were diagnosed as having mechanical infertility, and abnormal hysteroscopic findings were observed in 32 (21%). Forty-one women were diagnosed as having unexplained infer-tility (18%) and six (15%) had abnormal findings with hysteroscopy. Of the 30 couples who entered the in vitro fertilization regimen program because of male infertility, 4 (13%) had abnormal findings. The overall rate of abnormal findings was 19%; cervical canal and intrauterine abnormalities were found in 10 and 32 patients, respectively. Ten patients were treated during hysteroscopic evaluation procedure, and four patients subsequently underwent operative hysteroscopy under general anesthesia. We suggest that diagnostic hysteroscopy should be a routine procedure before in vitro fertilization and embryo transfer therapy.     

A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles

Objective: To compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET.

Design: Randomized, open-label study.

Setting: Academic medical center.

Patient(s): Two hundred and one women undergoing IVF-ET.

Intervention(s): Women were randomized to supplementation with Crinone 8% (90 mg once daily) or IM progesterone (50 mg once daily) beginning the day after oocyte retrieval.

Main Outcome Measure(s): Pregnancy, embryo implantation, and live birth rates.

Result(s): The women randomized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy (48.5% vs. 30.4%; odds ratio [OR], 2.16; 95% confidence interval [CI], 1.21, 3.87), embryo implantation (24.1% vs. 17.5%; OR, 1.89; 95% CI, 1.08, 3.30), and live birth rates (39.4% vs. 24.5%; OR, 2.00; 95% CI, 1.10, 3.70) than women randomized to Crinone 8%.

Conclusion(s): In women undergoing IVF-ET, once-a-day progesterone supplementation with Crinone 8%, beginning the day after oocyte retrieval, resulted in significantly lower embryo implantation, clinical pregnancy, and live birth rates compared with women supplemented with IM progesterone.     

Satellite in vitro fertilization: The Oregon experience

Objective: This study was designed to compare the results of preliminary evaluation, ovarian hyperstimulation, and monitoring of patients at a distant in vitro fertilization satellite center with those treated at the main campus of the program.Study design: Fifty-four patients completing oocyte retrieval cycles at the Eugene satellite Oregon Health Sciences University in vitro fertilization program for the period Jan. 1, 1991, through Dec. 31, 1993, were compared with 222 patients at the main campus for age, peak estradiol level, number of oocytes, retrieved, number of embryos, clinical pregnancy rate, and pregnancy outcome.Results: There were no statistically significant differences between the Eugene in vitro fertilization satellite center and the main campus for any of the factors analyzed with the exception of clinical pregnancy rate. The clinical pregnancy rate per cycle at the Eugene satellite center was 39% while the Portland main campus rate was 23% (p = 0.027), presumably because of a larger number of couples with severe male factor infertility at the central site.Conclusion: A distant in vitro fertilization satellite program was highly successful in the Oregon experience. In addition to greater convenience to the patients, the program was highly comparable to main campus program in measured parameters of ovarian hyperstimulation, oocyte retrieval, number of embryos, and pregnancy rate.     

Ovulation induction and luteal support with GnRH agonist in patients at high risk for hyperstimulation syndrome

Abstract

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75–150 UI/day were started on day 2–5, GnRH antagonist was added when the lead follicle was >14?mm and the final trigger was obtained with hCG 250?µg or triptorelin 0.2?mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.