Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Delaying the initiation of progesterone supplementation until the day of fertilization does not compromise cycle outcome in patients receiving donated oocytes: a randomized study. Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer. Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study. Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing progesterone for IVF and oocyte donation. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova. A prospective randomized study: day 2 versus day 5 embryo transfer. Local injury to the endometrium on the day of oocyte retrieval has a negative impact on implantation in assisted reproductive cycles: a randomized controlled trial. The use of gonadotrophin-releasing hormone analogues in women receiving oocyte donation does not affect implantation rates. Progesterone supplementation during cryopreserved embryo transfer cycles: efficacy and convenience of two vaginal formulations. The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation. The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization. Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome. The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer.
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. To determine whether the initiation of P supplementation as artificial luteal phase support (day -1, day 0, or day +1 of egg donation) in extensive programs of ovum donation influences cycle cancellation, pregnancy outcome, and implantation rate in day 3 embryo transfers.
                Prospective randomized trial.
                Oocyte donation program at the Instituto Valenciano de Infertilidad, Valencia, Spain.
                Three hundred recipients with normal ovarian function, absence of uterine anomalies, and undergoing their first egg donation were recruited between September 2003 and September 2004.
                A computer-based randomization divided the recipients into three groups when hCG was administered to their matched donors. The first group (group A) started P supplementation the day before oocyte retrieval; the second group (group B) started P supplementation on the day of the oocyte retrieval; and the third group (group C) started P supplementation 1 day after the egg retrieval once fertilization was confirmed.
                Implantation, pregnancy, and ongoing pregnancy rates were the primary outcome measures considered. The secondary outcome measure was the cancellation rate, especially due to fertilization failure.
                Global cancellation rate and cancellation rate due to fertilization failure were significantly higher in group A (12.4% and 8.2%, respectively) than in group C (3.3% and 0%, respectively). Reproductive outcome was similar in all the groups except for a higher biochemical pregnancy rate in group A (12.9%) than in groups B (6.6%) and C (2.3%).
                Initiation of P on day +1 of embryo development decreases cancellation rates of day 3 embryo transfers in extensive programs of ovum donation without any deleterious effect on pregnancy outcome or implantation rate. 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. 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. A polysyloxane vaginal ring containing 1g of natural progesterone was developed as luteal supplementation for women treated with IVF-embryo transfer and for agonadal women participating in an oocyte donation programme. The ring provides continuous release of progesterone (10-20 nmol/l) for 90 days. The efficacy of this form of progesterone supplementation was evaluated in two multicentre prospective randomized trials. IVF-embryo transfer trial: After oocyte aspiration, 505 women were randomly allocated to progesterone supplementation with vaginal ring or i.m. progesterone (50 mg/day). The clinical pregnancy rate was 36.6% in both groups. Implantation rate was 15.9% in the vaginal ring and 16.0% in i.m. progesterone. Oocyte donation trial: After endometrial proliferation with micronized oestradiol, 153 women were allocated to progesterone replacement with a vaginal ring or i.m. progesterone (100 mg/day). Clinical pregnancy rate was 39.8 and 28.6% respectively. Implantation rate was significantly higher with the vaginal ring compared with i.m. progesterone (19.9 and 11.6% respectively, P = 0.006). The vaginal ring is a novel development which provides continuous release of progesterone for 90 days. In IVF-embryo transfer, its effectiveness is similar to daily i.m. injections. In oocyte donation the ring provides a progestative milieu which improves the implantation rate and eliminates the discomfort of daily i.m. injections. To compare the efficacy of a vaginal progesterone preparation with our standard IM preparation within a donor egg program.
                Prospective randomized trial.
                Donor egg program at a university assisted reproductive therapy program (Jones Institute for Women's Health).
                Couples accepted into the donor egg program because of either premature ovarian failure or evidence of diminished ovarian reserve.
                Women were randomized into either a group receiving IM progesterone replacement or a group receiving vaginal progesterone replacement. Both groups underwent Estraderm patch/progesterone treatment in a mock cycle leading to an endometrial biopsy on day 26 followed by a second cycle in which ET was performed. Subjects with residual ovarian function received a GnRH agonist. In the IM treatment group, 100 mg was administered from cycle days 15 to 27. In the vaginal treatment group, Crinone 8%, a polycarbophil-based gel preparation containing 90 mg of micronized progesterone, was administered twice daily from the evening of day 14.
                Endometrial histology, serum levels of progesterone (on days 13, 17, 20, 24, and 26), the occurrence of pregnancy, implantation rate, and pregnancy outcome.
                Fifty-four women randomized into the vaginal progesterone treatment group and 18 women in the IM treatment group achieved ET. Mean serum progesterone levels were higher in the IM treatment group than in the Crinone group. Endometrial histology was "in phase" for all subjects in both groups. Clinical pregnancies were observed in 26 of 54 women and 5 of 18 women in the Crinone and IM progesterone groups, respectively. The ongoing pregnancy rate (PR) of 31% (17/54) and implantation rate of 23% in the subjects receiving Crinone was not statistically different from the IM progesterone group's ongoing PR of 22% (4/18) and implantation rate of 18%.
                Vaginal progesterone replacement with the polycarbophil gel preparation was as effective as IM progesterone in producing clinical and ongoing pregnancies within our donor egg program in the dosages administered. 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) This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers.
                Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred.
                The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%).
                This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers. To evaluate the effect of local injury to the endometrium on the day of oocyte retrieval on implantation and pregnancy rates in assisted reproductive cycles.
                In a prospective controlled trial, a total of 156 patients, <38 years old, in their first in vitro fertilization (IVF) cycle were randomized. In 77 patients, two small endometrial samples from anterior and posterior walls of uterus were obtained with a Novak curette on the day of oocyte retrieval and in 79 patients no intervention was performed.
                The experimental and control patients were matched regarding women's age, body mass index, basal FSH, duration and etiology of infertility, treatment protocol, number of retrieved oocyte, endometrial thickness, percentage of intracytoplasmic sperm injection performance, fertilization rate, the percentage of patients with good and top quality embryos, and the number of embryos transferred. The implantation rate (7.9 vs. 22.9%), clinical (12.3 vs. 32.9%; odds ratio = 0.25; 95% confidence interval = 0.12-0.66; p < 0.05) and ongoing pregnancy (9.6 vs. 29.1%; odds ratio = 0.25; 95% confidence interval = 0.10-0.64; p < 0.05) rates were significantly lower in experimental group, compared with 79 controls.
                According to the results of this study, local injury to the endometrium on the day of oocyte retrieval disrupts the receptive endometrium and has a negative impact on implantation and IVF outcomes. There is conflicting clinical evidence suggesting a positive role for gonadotrophin-releasing hormone analogues (GnRHa) on implantation in humans. This potential effect was evaluated in this study taking the oocyte donation programme as a model. Patients were randomly allocated into one of the two treatment groups: group I received simultaneous treatment with GnRHa and steroids, and group II only received exogenous steroid replacement. An analysis of the donors and semen quality showed similarity between recipient groups. There was no significant difference between groups in the number and quality of embryos replaced, clinical pregnancy and implantation rates. In summary, using a model in which the endometrium can be analysed independently of the embryos, the results suggest that GnRHa are neither effective nor detrimental for embryo implantation in humans. Sequential exogenous oestradiol and progesterone are often used to prepare the endometrium in frozen embryo transfer (FET) cycles. This open-label, randomized study compared the efficacy and acceptability of self-administered once daily vaginal progesterone gel and vaginal micronized progesterone tablets (three times daily) for luteal support in FET cycles. An Asian population of women (aged < or = 45 years) were assigned randomly to receive progesterone gel (90 mg, once daily, n= 100) or vaginal micronized progesterone tablets (200 mg, three times daily, n= 100). All received oestradiol from day 2 of the menstrual cycle, for at least 10 days (or until endometrial thickness was > or =8 mm), before self-administering progesterone for 2 days before FET and up to 14 weeks afterwards if pregnancy occurred. Clinical pregnancy rates (31% for gel and 28% for tablets) and implantation rates (9.8% and 8.8%, respectively) were not significantly different between the treatment groups. Asian women using once daily progesterone gel found the gel easy to use and comfortable, and preferred it to their previous experience of vaginally administered tablets. In summary, once-daily vaginal progesterone gel has similar efficacy to vaginal tablets and is associated with high patient satisfaction. Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for pituitary desensitization may impair the outcome of IVF as compared to classical short-acting formulations. Whether the negative effects are directed against the corpus luteum, the endometrium, or both is unknown. However, the presence of high affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human endometrium suggests a possible role of these analogues on this target organ, affecting embryo implantation. In the present study, we tested direct effects of two different forms of GnRHa on implantation using the ovum donation model. Patients were prospectively allocated to one of the three study groups: the short-acting form of the analogue leuprolide acetate (group I; n=64), the long-acting form of the same analogue (group II; n=58), and the long-acting preparation of the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo transfer was carried out in group I, whereas 67 were performed in group II and 65 in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because of bleeding while being on the waiting list for anonymous oocyte donation. The number of oocytes donated, fertilization rates and embryos replaced in each group were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6% respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1 and 17.0%. These data suggest that the use of a long-acting form of GnRHa provides success rates similar to the short-acting preparations, resulting in more convenient medication for patients with ovarian function included in ovum donation programmes. To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle.
                Prospective randomized study.
                Ninety-one patients having their first attempt at IVF.
                Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle.
                The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2.
                The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF. To compare the efficacy of administration i.v. albumin to prevent severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing ovarian stimulation for IVF with a standard policy of cryopreserving all embryos and to assess the impact of the two methods of treatment on pregnancy rates (PRs).
                Prospective randomized study.
                A tertiary referral center for assisted conception.
                Twenty-six patients undergoing IVF treatment cycles who were considered to be at high risk of developing severe OHSS on the basis of their serum E2 concentrations on the day of hCG administration and the number of oocytes collected.
                In group 1 (n = 13) all the generated embryos were cryopreserved to be transferred subsequently in hormonally manipulated cycles. In group 2 (n = 13) patients received IV infusions of albumin on the day of oocyte retrieval and 5 days later. Patients in group 2 had transfers of fresh embryos.
                The total dosage of hMG used, total number of follicles developed, number of follicles > 14 mm in diameter, serum E2 concentrations and endometrial thickness on day of hCG administration, number of oocytes retrieved, number and quality of embryos generated, PRs per cycle commenced, and onset and degree of any OHSS developed.
                There were no significant differences in the above parameters between the two groups, except for PRs that were significantly higher in patients who had all embryos cryopreserved (38.6% versus 0%).
                The policy of cryopreserving all generated embryos appears as effective as the administration of i.v. albumin in preventing OHSS in high-risk patients and produces significantly higher PRs. To examine the relationship between endometriosis and preclinical abortions and to evaluate the effect of gonadotropin-releasing hormone analogue (GnRH-a) therapy on these pregnancies.
                Of 67 women with severe endometriosis referred to us for in vitro fertilization-embryo transfer (IVF-ET), 32 underwent ovarian stimulation for oocyte retrieval with menotropins (protocol A), whereas the other 35 were admitted for the procedure after a 6-month period of hormonal suppression with a GnRH agonist (protocol B). The clinical impact of the preclinical and clinical pregnancies in both treatment protocols were evaluated on the basis of oocyte classification and embryo quality score.
                All patients were treated in our IVF Unit.
                Clinical pregnancy was used as our main outcome measure of success.
                A significantly higher number of preclinical pregnancies (P less than 0.0001) occurred in patients treated by protocol A. After GnRH-a treatment, the preclinical pregnancy rate declined significantly (P less than 0.0001), whereas the clinical pregnancy rate per cycle and per transfer rose significantly (P less than 0.0001 and P less than 0.0001, respectively). Furthermore, clinical pregnancies had a significantly better mean embryo quality score in comparison with preclinical pregnancies (P less than 0.0001).
                It is concluded that combining GnRH-a therapy before IVF-ET provides an improved treatment modality for preclinical abortions and infertility associated with severe endometriosis.
There is insufficient evidence to recommend any one particular protocol for endometrial preparation over another with regard to pregnancy rates after embryo transfers. These were either frozen embryos or embryos derived from donor oocytes. However, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation is commenced prior to oocyte retrieval in oocyte donation cycles. Adequately powered studies are needed to evaluate each treatment more accurately.