Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study. Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer. Pituitary suppression in ultrasound-monitored frozen embryo replacement cycles. A randomised study. Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova.
Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost. To test the efficacy of endometrial preparation with exogenous steroids, without pretreatment with gonadotropin-releasing hormone (GnRH) agonist, in women with normal ovarian function.
                Prospective randomized study.
                Private outpatient infertility clinic.
                Two hundred ninety-six women undergoing frozen-thawed embryo transfer.
                In group 1 (146 patients), depot GnRH agonist was administered in the luteal phase; treatment with 17beta-estradiol transdermal patches at steadily increasing dosage from 100 to 300 microg was then given for at least 12 days. In group 2 (150 patients), endometrial preparation began on day 1 of menstrual cycle. The starting dose was 200 microg; this was increased to 300 microg after 7 days.
                Pregnancy, abortion, implantation and cancellation rates.
                In group 2, six cycles (4%) were cancelled due to evidence of ovulation. Groups were similar in the percentage of embryos that survived freezing-thawing (77.1% in group 1 and 76.6% in group 2) and in the number of embryos transferred per patient (2.1 +/- 0.6 and 2.1 +/- 0.7, respectively). Groups 1 and 2 did not differ significantly in rates of pregnancy (19.7% and 24.1%), abortion (17.8% and 11.7%), and implantation (10.4% and 11.9%).
                Endometrial preparation for frozen-thawed embryo transfer based exclusively on steroid administration appears to be as effective as the more conventional protocol involving preliminary desensitization with a GnRH agonist. This simplified protocol reduces costs, minimizes pharmacologic treatment, and increases patient compliance. The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates. This study was designed to assess the value of using a gonadotrophin-releasing hormone (GnRH) agonist prior to exogenous steroid supplementation for endometrial preparation in frozen-thawed embryo replacement (FER) cycles.
                A prospective randomized trial of 234 patients undergoing FER cycles was conducted. The study population was randomly divided into two groups according to a computer-generated list. In group A (n = 117), a daily dose of 6 mg of oral estradiol valerate was initiated on menstrual day 1 following pituitary suppression using 400 mcg buserelin acetate daily. In group B (n = 117), the same dose of estradiol valerate was initiated on day 1 of bleeding without prior GnRH agonist therapy. In both groups, ovulation monitoring was not undertaken and progesterone pessaries (800 mg daily) were administrated when the endometrial thickness had reached 8 mm or more with embryo transfer taking place 2 days later.
                The two groups were comparable with respect to cause of infertility, age at stimulation (32.8 +/- 4 vs 33.2 +/- 3.9 years, P = 0.4), basal FSH level (6.3 +/- 1.7 vs 6.4 +/- 2 IU/l, P = 0.5), number of oocytes collected (16.9 +/- 7.3 vs 16.5 +/- 7.4, P = 0.7) and fertilized normally in the retrieval cycle (11.5 +/- 4.9 vs 11 +/- 4.9, P = 0.4) and number of embryos cryopreserved (6.6 +/- 3.6 vs 6.2 +/- 3.6, P = 0.3). There was no significant difference between the two groups in age at frozen replacement (33.6 +/- 4.2 vs 34 +/- 3.9 years, P = 0.4), duration of the proliferative phase (20.7 +/- 8.6 vs 21 +/- 9.2 days, P = 0.7) and number of thawed embryos replaced (2.3 +/- 0.6 vs 2.2 +/- 0.6, P = 0.2). However, compared with group B, group A achieved significantly higher pregnancy (37.6% vs 24%, OR 1.8, 95%CI 1.1-3.4), clinical pregnancy (24% vs 11.3%, OR 2.5, 95%CI 1.2-5.5) and live birth rates (20% vs 8.5%, OR 2.9, 95%CI 1.2-8).
                Medicated frozen embryo replacement cycles timed by endometrial thickness measurement alone without monitoring or suppression of ovarian activity are associated with reduced outcome. In a prospective randomized study, the effect of two ovulation induction regimens on implantation rate of frozen/thawed pronucleate ova was investigated. Patients received either human menopausal gonadotrophin (HMG) or clomiphene/HMG. Ovulation induction was done on an individual basis using ultrasound and plasma 17 beta-oestradiol concentrations. Ovulation was induced with human chorionic gonadotrophin (HCG) when the leading follicle reached a diameter of 18 mm. Pronucleate ova had been frozen using the slow-freezing method of Lassalle et al. (1985) (Fertil. Steril., 44, 645-651) and were thawed in synchrony with the age of the endometrium. Both groups of patients were comparable for age, indication for in-vitro fertilization, pre-ovulatory 17 beta-oestradiol concentration, number of large follicles and number and quality of embryos transferred. The only difference found was that HCG was administered 1 day earlier in the HMG group compared to the clomiphene/HMG group (P < 0.01). Using univariate analysis, the pregnancy rate was higher in patients stimulated with HMG alone compared to those stimulated with clomiphene/HMG (27 versus 15% respectively; P < 0.03), when HCG was administered later in the menstrual cycle (P < 0.01) and when more and better quality embryos were transferred (P < 0.01). Using multivariate regression analysis, the influence of the stimulation on pregnancy rate was even more pronounced (P < 0.01) when the day of HCG administration and the number and quality embryos transferred were taken into account. Therefore, we conclude that HMG alone increases pregnancy rate compared to clomiphene/HMG during replacement cycles of frozen/thawed pronucleate ova. These data suggest that HMG results in a better endometrium receptivity for embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
At the present time there is insufficient evidence to support the use of one intervention in preference to another.