A comparative study of three ovulation induction protocols in polycystic ovarian disease patients in an in vitro fertilization/embryo transfer program

Purpose This study compares the results of three ovulation induction protocols in polycystic ovarian disease (PCOD) patients undergoing an in vitro fertilizationembryo transfer (IVF-ET) program. A total of 85 cycles was studied. The patients were treated with clomiphene citrate (CC) plus human menopausal gonadotropin (hMG) (CC/hMG group), with purified menofollitropin (pFSH) plus hMG (pFSH/hMG group), and with pFSH/hMG plus gonadotropin releasing hormone analogue (GnRH-a) (analogue group). In the analogue group the suppression of luteinizing hormone (LH) with GnRH-a decreased the number of follicles <12 mm on the day of human chorionic gonadotropin (hCG) administration and the number and percentage of immature oocytes retrieved and increased the percentage of mature oocytes retrieved.Results However, fertilization rates of oocytes, cleaved embryo rates, pregnancy rates following replacement, and pregnancy outcomes were not different.Conclusion Although the suppression of the hypothalamic-pituitary-ovarian axis with GnRH-a in PCOD patients improved follicular synchrony and oocyte maturity, none of the ovulation induction protocols was superior to the others with respect to pregnancy rates and pregnancy outcomes.     

An increased initial follicle-stimulating hormone/luteinizing hormone ratio does not affect ovarian responses and the outcomes of in vitro fertilization

The tenet that a combination of human follicle-stimulating hormone (hFSH)/human menopausal gonadotropin (hMG) improves follicular recruitment was assessed by randomly treating ovulatory women either with hFSH/hMG on days 3 and 4 of the cycle followed by two ampules of hMG daily or with a constant daily dose of 2 ampules of hMG. Estradiol (E2) levels on the day of human chorionic gonadotropin (hCG) and the mean number of mature, immature and atretic oocytes per cycle did not differ between the two groups. Likewise, fertilization, cleavage, and pregnancy rates were similar for the two treatments. When daily hormone levels were compared in 11 patients during two successive treatment cycles with both stimulation protocols, the temporal pattern of FSH accumulation was repeated in both cycles, but FSH levels were significantly higher when patients received hFSH/hMG. Nevertheless, during both cycles, E2 reached similar peak levels and the mean number of follicles per cycle on the day of hCG administration was not different. We conclude that routine use of hFSH/hMG does not improve the success of an in vitro fertilization (IVF) program and that higher FSH levels do not change the individuality of ovarian response in the same woman.     

Preliminary experince with a combination of clomiphene and variable dosages of menopausal gonadotropins for enhanced follicular recruitment

A combination of clomiphene citrate and human menopausal gonadotropin was employed for enhanced follicular recruitment in an in vitro fertilization program. All patients received 50 mg of clomiphene and 1 ampule of human menopausal gonadotropin daily from cycle day 5 through cycle day 9. Follicular monitoring was begun on day 10 using a combination of ultrasound measurement of follicular size and number and determination of peripheral estradiol levels. Based on the size and number of follicles, the peirpheral levels of estradiol, and the rate of follicular growth and increase in estradiol, human menopausal gonadotropin was continued at a dosage of 1 to 3 ampules/day through the day of human chorionic gonadotropin administration. Human chorionic gonadotropin was administered on the evening of the day the largest follicle reached or exceeded 20 mm in mean diameter if the estradiol levels had been rapidly rising or reaching a plateau and had exceeded a minimal level of 300 pg/ml. Using this protocol, 30 of 33 patients underwent laparoscopy, 29 patients had successful oocyte recovery, and 23 patients underwent embryo replacement, with the establishment of six clinical pregnancies.     

Results of in vitro fertilization cycles in women aged 43-45 years.

Our objective was to evaluate the results of in vitro fertilization (IVF) cycles in the elderly (43-45 years old) female population. All consecutive women aged 43-45 years admitted to our IVF unit from January 1996 to December 2001 were enrolled in the study. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred and pregnancy rate were assessed. Seven hundred and eight consecutive IVF cycles in 276 patients were evaluated. Two hundred and seven cycles were cancelled (cancellation rate 29.2%). Forty-seven patients achieved a clinical pregnancy (pregnancy rate 6.6% per cycle and 9.4% embryo transfer) with a 30% live birth rate. In patients who underwent embryo transfer, there were no differences between conception and non-conception cycles in patient's age, number of gonadotropin ampules used, length of ovarian stimulation, number of oocytes retrieved, fertilization rate or cleavage rate. However, the conception cycles were associated with a significantly lower peak estradiol level (p < 0.04) and higher number of total (p < 0.03) and good-quality (p < 0.005) embryos transferred, in addition to a lower ratio of estradiol level/number of follicles > 14 mm on day of human chorionic gonadotropin administration and of estradiol level/number of oocytes retrieved. We conclude that, although older female age is a major contributor to IVF failure, successful IVF cycles can be expected in patients aged 43-45 years in the presence of low ratios of peak estradiol to either number of follicles > 14 mm on day of human chorionic gonadotropin administration or number of oocytes retrieved that reach the stage of embryo transfer with at least two good-quality embryos.     

The relationship between follicular fluid steroid concentration and successful fertilization of human oocytes in vitro

Follicular fluids (FF) and their matched oocytes were obtained from 64 follicles of 28 women who failed to conceive after in vitro fertilization ( IVF ) and 33 follicles of 8 women who successfully conceived after the procedure. Ovulation was induced with human menopausal gonadotropin, and follicular aspiration was performed 36 hours after human chorionic gonadotropin administration. The concentration of 17 beta-estradiol, progesterone, testosterone, dihydrotestosterone, and androsterone was correlated with the morphology of the oocyte-corona-cumulus complex ( OCCC ), oocyte fertilization, the rate of cleavage, and the incidence of pregnancy after embryo transfer. In both groups of women, FF progesterone was lowest in follicles containing immature OCCCs . However, follicles aspirated from women who conceived after IVF which contained intermediate and mature OCCCs had significantly higher FF estradiol levels than similar follicles from women who failed to conceive after the procedure. Fertilized oocytes and 4- to 6-cell stage embryos which were obtained from follicles of pregnant women contained significantly higher FF estradiol levels than fertilized oocytes and similar embryos from nonpregnant women. It appears that higher FF estradiol levels correlate well with successful fertilization and an enhanced cleavage rate of oocytes associated with pregnancy following IVF .     

Endocrine changes in the late-follicular and postovulatory intervals as determinants of the in vitro fertilization pregnancy rate

This investigation examines the hormone pattern in in vitro fertilization (IVF) cycles from the time of human chorionic gonadotropin (hCG) administration through embryo transfer to ascertain whether the absolute levels or secretory patterns of the major reproductive hormones affect the IVF pregnancy rate. Thirty-one women who underwent IVF treatment were enrolled in the study. All patients received clomiphene citrate/human menopausal gonadotropin for ovulation induction. Significant elevations in serum estradiol (E2) levels in the pregnant group were found throughout the cycle interval studied. After hCG administration the serum hCG levels were not different between the groups. Significant elevations in serum progesterone (P) concentrations were found in the pregnant group from the day after laparoscopy through embryo transfer. Embryos obtained from the pregnant group appeared to be different in that the mean number of blastomeres per embryo transferred was significantly greater. Therefore for achievement of an IVF pregnancy the optimal hormone pattern employing combination ovulation induction in the ovulation to transfer interval is a relatively high E2 level in ovulation followed by a high P level at transfer and into the luteal phase. These elevated hormone levels do not depend on the response to exogenous hCG.     

Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection

OBJECTIVE: To investigate the effect of continuous administration of gonadotropin-releasing hormone agonist (GnRHa) during the luteal phase in an intracytoplasmic sperm injection program. STUDY DESIGN: One hundred eighty-one women underwent a down-regulation protocol of GnRHa administered from the 21st day of the preceding cycle. Patients were randomized at initiation of stimulation by a computer-generated list. Group 1 patients (n = 90) were continuously administered GnRHa for 12 days after embryo transfer, while in group 2 patients GnRHa was stopped on the day of human chorionic gonadotropin administration. RESULTS: Demographic parameters, infertility etiologies, number of gonadotropin ampules used, number of mature oocytes recovered, rates of testicular sperm usage, number of embryos transferred, and cycle and transfer cancellation rates were similar in both groups. Clinical pregnancy rates, implantation rates and live birth rates did not show a significant difference. CONCLUSION: Extending GnRHa treatment through the luteal phase appeared not to have a significant impact on pregnancy or implantation rates in intracytoplasmic sperm injection cycles.     

The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study.

OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or placebo were administered in a prospective randomized double-blind manner. PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. CONCLUSIONS: In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.     

A preliminary study on in vitro fertilization and embryo transfer

Forty-two women with infertility were enrolled in an in vitro fertilization and embryo transfer (IVF/ET) program, from July, 1986 to February, 1988, at the First Affiliated Hospital, Human Medical University. CC/hMG/hCG and hMG/hCG regimens for ovulation induction were used for 35 and 7 patients. Monitoring methods consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin 10,000IU was administered when the leading follicle reached 18mm in diameter and serum E2 level was equal to or more than 1,480 pmol/L (400 pg/ml). Twenty-one laparoscopies and nineteen laparotomies for oocyte retrieval were performed. The IVF/ET results using CC/hMG/hCG for ovarian stimulation were as follows: an average of 6.1 follicles were aspirated and 3.5 oocytes recovered for one case. The recovery rate and fertilization rate was 57.0% and 60.1% respectively. In twenty-five women one to five embryos were transferred and a clinical pregnancy occurred in one who received three embryos. Laparotomy for oocyte retrieval showed that more oocytes could be obtained than laparoscopy. The purity of CO2 used for laparoscopy was considered to affect the IVF results.     

Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone.

OBJECTIVE: To compare the in vitro fertilization and embryo transfer (IVF-ET) outcome of a 3-day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. DESIGN: Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. SETTING: The IVF-ET program. MAIN OUTCOME MEASURES: Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. RESULTS: The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. CONCLUSION: The ultrashort protocol, although being convenient and having some advantages found in the long GnRH-a protocol, is inferior in its outcome compared with the two other protocols.     

Pregnancy rates in varying age groups after in vitro fertilization: a comparison of follitropin alfa (Gonal F) and follitropin beta (Follistim)

OBJECTIVE: Our purpose was to assess the efficacy of two recombinant follicle-stimulating hormones, follitropin beta (Follistim, Organon, West Orange, NJ) and follitropin alfa (Gonal F, Serono, Norwell, Mass) on pregnancy rates in varying age groups of women undergoing in vitro fertilization (IVF). STUDY DESIGN: Three hundred sixty-five IVF cycles were retrospectively compared, 233 by use of follitropin beta and 132 by use of follitropin alfa, both after gonadotropin-releasing hormone agonist down-regulation. Assignment to each medication was indiscriminate. The primary outcome measured was pregnancy evidenced by fetal heartbeat on ultrasonography. Secondary outcomes included days of stimulation, ampules per patient cycle, estradiol level on the day of human chorionic gonadotropin administration, total follicles present on the day of human chorionic gonadotropin administration, follicles greater than 14 mm, oocytes retrieved, mature eggs, fertilization rate, and embryos transferred. Outcomes were stratified by age, including women less than 36 years old, 36 to 39 years old, and more than 39 years old. RESULTS: There was no significant difference between follitropin beta and follitropin alfa in either the primary or secondary outcomes, although the pregnancy rate was significantly decreased with advancing age. CONCLUSION: Success rates are similar, when stratified by age, in women undergoing IVF with either follitropin beta or follitropin alfa.     

The use of high-dose human menopausal gonadotropin in an in vitro fertilization program

Sixty-three normal ovulatory women suffering from obstructive tubal disease not corrected by previous surgery were enrolled in an in vitro fertilization (IVF) program. To achieve a large number of mature follicles, a relatively high dose of human menopausal gonadotropin (hMG) was administered (19 +/- 4 ampules/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (10,000 IU) was administered when more than two large follicles (1.6 to 1.8 cm in diameter) were visualized. Fifty-five laparoscopies for oocyte retrieval were performed. A mean of 4.3 follicles per woman were aspirated, and 3.2 oocytes per woman were recovered. The oocytes were preincubated for 8 or 24 hours according to the morphologic degree of mucification and dispersal of the oocyte-corona-cumulus complex. Seventy-seven percent of the oocytes were fertilized and were transferred into the uterus 38 to 40 hours after insemination. Fifty-two women received one to eight embryos (mean, 3.5 +/- 1.9), and 9 (17%) conceived. This regimen of high-dose hMG precludes the need for serum or urine luteinizing hormone monitoring, because the occurrence of spontaneous ovulation is low. It is valuable in increasing the number of fertilizable oocytes, the percentage of women undergoing embryo transfer, and compensates with multiple oocyte transfer for the high embryonic loss involved in IVF.     

Dose of human menopausal gonadotropin influences the outcome of an in vitro fertilization program

This study compares outcomes of in vitro fertilization (IVF) in two groups of 57 patients when either 2 (group 1) or 3 (group 2) ampules of human menopausal gonadotropin (hMG) were administered daily. Treatment began on day 3 of the cycle and was discontinued when at least 2 follicles attained diameters greater than or equal to 1.5 cm. Human chorionic gonadotropin (hCG) was given either 24 or 48 hours after the last dose of hMG. Although serum estradiol levels were lower in group 1, the average number of oocytes retrieved (3.2 versus 2.9), fertilized (1.9 versus 2.0), and cleaved (1.7 versus 1.8) per completed cycle did not differ between groups 1 and 2. Likewise, the number of oocytes that fertilized abnormally was similar in both groups (0.5 versus 0.3/cycle). However, the number of atretic oocytes (0.03 versus 0.5/cycle) and the percent of oocytes recovered from the cul-de-sac (0 versus 7.2%) were significantly (P less than 0.05) lower in group 1. In group 1, administration of hCG 48 hours after the last dose of hMG was associated with a higher number of cleaving embryos (2.1 versus 1.5/cycle) and a higher pregnancy rate (34.8 versus 14.7%; P less than 0.05) when compared with injection at 24 hours. In group 2, the interval between hMG and hCG did not influence these results. Together, the associations between fewer oocytes that were atretic or recovered from the cul-de-sac, and a trend toward a higher pregnancy rate, suggest that follicular recruitment with 2 ampules of hMG is more appropriate than 3 ampules in an IVF program.     

An in vitro fertilization and embryo transfer pilot study: treatment-dependent and treatment-independent pregnancies

A pilot program of in vitro fertilization and embryo transfer at McMaster University is described. Fourteen couples with a clinical diagnosis of infertility due to apparent tubal dysfunction, with evidence of ovulation, and with normal semen analysis underwent induction of superovulation with human menopausal gonadotropin. At laparoscopy, 82 follicles were aspirated and 19 oocytes were recovered. Eleven oocytes demonstrated cleavage and all inseminated oocytes were transferred 49 to 65 1/2 hours after insemination. In vitro fertilization therapy resulted in two pregnancies, one leading to a spontaneous abortion and the other to the birth of a healthy female infant. At 10 to 12 months after in vitro fertilization therapy in the remaining 12 patients, there were three additional pregnancies (treatment-independent), one ectopic and two intrauterine. One patient was delivered of a healthy female infant. In vitro fertilization therapy should be evaluated by a randomized controlled clinical trial.     

A preliminary trial of human zygote culture in Ham's F-10 without hypoxanthine

Purpose This study deals with the suitability of Ham's F-10 without hypoxanthine for early cleavage-stage embryo culture. A high percentage of mouse two-cell embryos developed into morula and blastocysts in Ham's F-10 formulated without hypoxanthine (75.3 and 71.6%, respectively); in contrast, in agreement with previous reports, only 15.4% developed beyond the two-cell stage in Ham's F-10 with hypoxanthine. To begin to evaluate the effect of hypoxanthine on human embryos, a total of 318 human oocytes was fertilized and cultured in Ham's F-10 minus hypoxanthine.Results The fertilization, cleavage, and pregnancy percentages in two ovulation induction protocols [human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) and gonadotropin releasing hormone/hMG/hCG] were 82, 88, and 20 and 83, 91, and 30%, respectively.Conclusion These results suggest that, in agreement with mouse embryo development, hypoxanthine does not appear to be necessary for human embryo cleavage and its omission from Ham's F-10 may enhance the conditions for culture of early-cleaving human embryos. These observations may lead to a better understanding of critical cell processes during early human embryonic development.     

The outcome of continued treatment of luteinizing hormone-surged cycles in in vitro fertilization with the use of human menopausal gonadotropin

Over a 2-year period 75 patients were treated for 109 cycles with human menopausal gonadotropin for in vitro fertilization. The occurrence of endogenous luteinizing hormone (LH) surges was monitored by daily blood sampling. Forty-six cycles (42%) showed an endogenous LH surge. Instead of canceling the treatment cycle as other programs do, we proceeded to oocyte collection when the surge was detected. Human chorionic gonadotropin was administered routinely to the "surge" patients as soon as the LH surge was determined. The oocyte collection was carried out around 24 hours after the "surge" blood had been drawn, although the beginning of the endogenous LH surge was unable to be pinpointed. Significantly more immature oocytes, lower fertilization rate, and lower cleavage rate were seen in the "surge" patients than in the "nonsurge" patients. In five "surge" cycles laparoscopy for oocyte collection was canceled, but none was canceled because of premature ovulation detected by the immediately preoperative ultrasonography. In four "surge" cycles no potentially fertilizable egg was recovered. This was not significantly different from that of the "nonsurge" group. The pregnancy rate of the "surge" group (4/41 or 9.8% per laparoscopy and 4/34 of 11.8% per embryo transfer) was not statistically different from that of the "nonsurge" group (7/61 or 11.5% per laparoscopy and 7/56 or 12.5% per embryo transfer). This study presents the possibility of proceeding to oocyte collection, fertilization, embryo transfer, and pregnancy in patients with endogenous LH surge in in vitro fertilization procedures with the use of human menopausal gonadotropin treatment.     

Human in vitro fertilization and embryo transfer at the University of Texas,Houston

The current clinical and laboratory protocols of the in vitro fertilization program at the University of Texas at Houston are described and detailed. Most patients treated have tubal disease, with a limited number of couples having male factors. Clomiphene citrate (50 mg/day, cycle days 5–9) with or without added menopausal gonodotropins is the principle agent for enhanced follicular recruitment. Follicular development is monitored primarily with daily ultrasonography, and human chorionic gonadotropin (hCG) is given when the largest follicle reaches or exceeds 20-mm mean diameter. The culture media used are modifications of Ham's F-10. Mature oocytes are preincubated for 5 hr before insemination with 50,000 motile sperm per oocyte. Using these protocls, the clinical pregnancy rate is 11.6% per laparoscopy (11/95) and 16.2% per embryo transfer (11/68).     

The effect of prolactin on murine in vitro fertilization and embryo development

Elevated levels of serum and follicular fluid prolactin occur in women undergoing ovulation induction with both clomiphene citrate and gonadotropin therapy. Prolactin's effect on oocyte fertilization and embryo cleavage has not been fully characterized. Using a murine model, we investigated the effect of prolactin on in vitro fertilization and subsequent embryo cleavage in media containing 150, 400, and 600 ng/ml purified mouse prolactin. No difference was found in fertilization rates when compared with control rates. Culture of both in vivo and in vitro fertilized two-cell embryos in murine prolactin at 150, 400, and 600 ng/ml showed no significant difference in blastocyst, morula, or embryo degeneration rates when compared with control rates. An assay for binding of murine prolactin to spermatozoa, oocytes, and the embryo at various cleavage stages revealed no specific murine prolactin binding. These in vitro experimental results fail to show a role for murine prolactin in effecting mature oocyte fertilization or subsequent embryo cleavage. The lack of binding of murine prolactin to the gametes and early developing embryo supports the in vitro findings.     

Clomiphene-HMG ovarian stimulation in human in vitro fertilization and embryo transfer

In a program for in vitro fertilization and embryo transfer, laparoscopies for oocyte aspiration were performed in 40 cycles in 36 normally menstruating women with irreparable tubal diseases (IVF patients) who received clomiphene citrate (CC) and human menopausal gonadotropin (hMG). An intramuscular injection of human chorionic gonadotropin (hCG) was given to all patients after completion of follicular maturation. Fourteen cycles in 13 spontaneously ovulating women (control patients), also stimulated with CC and hMG, were adequately monitored to identify the appearance of the spontaneous luteinizing hormone (LH) surge. The follicular maturation was followed by daily ovarian ultrasonographic examination and serum estradiol estimations. Just before the LH surge the diameter of the leading follicle was 20.2 +/- 0.7 (mean +/- S.E.) mm and the serum estradiol concentration per follicle was 384.1 +/- 16.3pg/ml in the control patients. In the IVF patients the former was 20.6 +/- 0.3mm and the latter was 305.8 +/- 13.3pg/ml prior to hCG administration. When the relationship of follicular size to the rates of oocytes recovery, maturation, fertilization and cleavage was examined, larger follicles (3ml less than or equal to follicular fluid volume) showed good results. Of the 152 oocytes that were recovered from these IVF patients, 96 (63.2%) were fertilized and 79 (52.0%) cleaved. Three pregnancies resulted from 35 embryo transfers.     

Advanced endometrial maturation after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin for in vitro fertilization

Endometrial biopsy was performed between the first and third luteal phase day in 22 normally cycling patients following human menopausal gonadotropin and human chorionic gonadotropin ovulation induction for in vitro fertilization but in whom embryo transfer was not accomplished. Eleven patients showed an "advanced" pattern and 10 an "in-phase" endometrium according to the Noyes criteria. A significant difference in serum progesterone levels on days 16 and 18 was found in these two groups. Serum progesterone levels were significantly higher by day 18 if pregnancy was established. In in vitro fertilization and embryo transfer the embryo arrives 24 to 48 hours earlier than in natural conception in the endometrial cavity. Therefore, the "advanced" endometrium may have some benefit for embryo implantation.