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.     

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.     

Delaying human chorionic gonadotropin administration in human menopausal gonadotropin-induced cycles decreases successful in vitro fertilization of human oocytes

Correct timing of human chorionic gonadotropin (hCG) administration in induced cycles for in vitro fertilization is of crucial importance to oocyte maturation and normal luteal function. The purpose of this work was to compare the effect of hCG timing on follicular development, oocyte maturation, and fertilization in vitro, as well as on the pattern of luteal phase hormone secretion. Ovulation was induced in 32 normally cycling women by human menopausal gonadotropin (hMG)/hCG administration. In the first group (17 women) 10,000 IU hCG was administered 24 hours after the last injection of hMG and in the second group (15 women) 48 to 72 hours after the last hMG injection. Serum estradiol levels prior to oocyte aspiration were similar in both groups, as were the numbers of large follicles on the day of hCG administration (4.5 +/- 2.3 versus 4.1 +/- 1.9 follicles/woman, respectively). The distribution of oocyte-corona-cumulus complexes was similar in both groups and was comprised of 11% immature, 43% intermediate, and 45% mature complexes. The fertilization rate, however, was significantly (P less than 0.001) reduced in the group treated by delayed hCG injection (57% versus 84%), and the percentage of degenerated oocytes was increased (9% versus 1%). Luteal phase length as well as progesterone and estradiol levels were comparable in both groups. It is concluded that an interval longer than 24 hours between the last injection of hMG and the administration of an ovulatory dose of hCG does not affect follicular and luteal phase serum steroid patterns but may result in a decreased oocyte fertilization rate, possibly due to atretic changes in the follicles.     

Ovarian stimulation with pure follicle-stimulating hormone/human menopausal gonadotropin and improved laparoscopic aspiration needles influence the success of an in vitro fertilization program

The effect of a combined pure follicle-stimulating hormone/human menopausal gonadotropin (pFSH/hMG) ovarian stimulation regimen and modified, sharpened laparoscopic follicular aspiration needles on the number of oocytes retrieved and the oocyte/follicle ratio in 43 consecutive cycles of in vitro fertilization (IVF) were retrospectively compared with 99 consecutive preceeding cycles stimulated with hMG alone and captured with aspiration needles that had never been sharpened. A modified laparoscopic follicular aspiration needle is described. Purified FSH/hMG ovarian stimulation significantly improved the mean serum estradiol levels, number of preovulatory follicles, and, therefore, the total number of oocytes recovered per cycle. The mean ratios of oocytes recovered per preovulatory follicle documented on ultrasound, and per aspirated follicle, increased significantly using sharpened needles. Both modifications improved the success rate of our IVF program.     

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.     

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 .     

Manipulating the follicular phase in IVF cycles: a comparison of two hMG stimulation protocols

The results of two human menopausal gonadotropin (hMG) protocols of ovulation induction for in vitro fertilization (IVF) were compared. With the first protocol, 28 women (group 1) were treated with an hMG dosage which was increased stepwise. With the second, 30 women (group 2) were treated with a high dose of hMG for 2 days, then given a constant daily dose. The two groups were compared with regard to ovarian response, luteal phase and laboratory and clinical outcomes of IVF. They were comparable as regards the total number of hMG doses required, the number of large follicles (mean diameter greater than 15 mm) on day 0 (day of human chorionic gonadotropin (hCG) administration), serum estrogen (E2) and progesterone (P) levels throughout the cycle and IVF laboratory and clinical outcomes. They differed significantly (p less than 0.01) only in the number of secondary smaller follicles (mean diameter less than 15 mm) observed on day 0 (3.7 +/- 0.4 for group 1 and 5.3 +/- 0.4 for group 2). Manipulating the hMG dosage during the early-mid follicular phase does not affect follicular synchrony, the number of oocytes harvested and the number of embryos achieved.     

Concomitant gonadotropin-releasing hormone agonist and menotropin treatment for the synchronized induction of multiple follicles

In an effort to overcome possible interference by endogenous gonadotropin-ovarian hormone dynamics, desensitization of the pituitary gonadotropins by a gonadotropin-releasing hormone agonist (GnRHa) was achieved in 12 women with repeatedly failed attempts at multiple follicular stimulation. Eight women were scheduled for in vitro fertilization (IVF) and embryo transfer (ET), and 4 for gamete intrafallopian transfer (GIFT). Stimulation failure was characterized by premature luteinization, poor estradiol (E2) response, or inadequate follicular growth. The agonist was administered by nasal spray 500 to 600 micrograms/day beginning on days 21 to 23 of the menstrual cycle. A rapid desensitization occurred by 7.6 +/- 0.6 days (mean +/- standard error [SE]) following the initial dose. Gonadotropin stimulation was begun when pituitary and ovarian suppression was judged to be adequate. In response to gonadotropin stimulation, a continuous rise of E2 was observed in all patients with a mean of 989 +/- 46 pg/ml on the day of hCG. A cohort of synchronized follicles was recruited and matured. The mean number of growing follicles per patient was significantly higher (P less than 0.0001) in combined therapy than in previously failed cycles (8.0 +/- 0.3 versus 3.2 +/- 0.1). All the patients underwent oocyte retrieval and 94.3% of the harvested oocytes were preovulatory. A high fertilization rate (89.7%) of the inseminated oocytes occurred in IVF patients.     

Inhibin activity of preovulatory follicles of gonadotropin-treated and untreated women

In order to determine whether treatment of endocrinologically normal women with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) led to alternations in follicular fluid inhibin activity and steroids, both inhibin activity and steroid levels were measured in follicular fluid of 10 follicles of 9 women treated with hMG/hCG and in follicular fluid of 15 preovulatory follicles of 15 untreated women. The women were given 150 IU hMG daily from day 3 until the serum estrogen levels were greater than 300 pg/ml, at which time hMG was discontinued and 10,000 IU hCG was given 50 hours later. Follicular fluid was aspirated from all visible follicles 36 hours after hCG. Women treated with hMG/hCG had multiple (two to five) follicles containing 1.5 to 4.5 ml of follicular fluid and a mature oocyte and elevated serum estrogen (400 to 800 pg/ml) on the day after hCG treatment. At the time of follicular fluid recovery, there was more inhibin activity (204 +/- 14 U/10 ml) in the hMG/hCG-stimulated follicles than in unstimulated follicles of a control group of women (65 +/- 14, mean +/- standard error, P less than 0.05). Follicular fluid from follicles of hMG/hCG-treated women had lower estrogen and progesterone levels, compared with normal preovulatory women. These data show that treatment of patients with hMG/hCG is associated with elevated follicular fluid inhibin activity.     

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.     

Human in vitro fertilization employing individualized ovulation induction by human menopausal gonadotropins

One hundred six women suffering from obstructive tubal disease not corrected by previous surgery were treated in an in vitro fertilization (IVF) program. Ovulation was induced by 3 amps of human menopausal gonadotropin (HMG)/day starting on the third day of the cycle for 5 days. In most of the patients the regmmen was continued for another 1–3 days, depending on the individual's ovarian response (means, 20±5 amps/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (HCG), 10,000 IU, was administered when more than two large (1.5 to 1.8 cm in diameter) follicles were visualized. Using this regimen, a mean of five follicles per woman was aspirated, from which a mean of 3.9 over was recovered. The oocytes were pre-incuted for 8 or 24 hr. according to the morphological degree of inucification and dispersal of the oocyte-corona-cumulus complex. Following exposure to washed spermatozoa for 16 hr, a 68% fertilization rate was obtained. Oocytes were transferred into the uterus 48 hr after laparoscopy. Ninety-nine transfers (93% of the women) of 1–8 embryos (mean, 2.9/woman) were performed and resulted in 16 clinical pregnancies. No pregnancies occurred in 14 women transferred with one to three oocytes in the pronuclear stage and only one pregnancy (7.1%) was obtained in 14 women transferred with one cleaved oocyte. Over 70% of the women were transferred with two or more cleaved oocytes: in this group the pregnancyl transfer rate was 21%. Of thee pregnant women 5 of 16 (31%) aborted between 6 and 10 weeks of gestation and 1 (6%) had an ectopic pregnancy. The individualized regimen of HMG is valuable in increasing the number of fertilized oocytes and compensates with multiple-embryo transfers for the high early embryonic loss occurring in IVF.     

The day of initiation of human menopausal gonadotropin stimulation affects follicular growth in in vitro fertilization cycles

The attainment of synchronous follicular development in human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization (IVF) continues to be a perplexing problem. Two regimens of follicle stimulation for IVF cycles were, therefore, compared. Twenty-nine patients commenced human menopausal gonadotropin (hMG) therapy on day I of the menstrual cycle (Group I), while 30 women received hMG from the third day of the cycle (Group II). The hMG therapy was tailored to the individual patients's response, based on ultrasonographic measurements of follicular size and serum estradiol (E₂) levels. Both groups of patients received a mean of 19.6±1.4 ampules of hMG over a mean of 6.1±0.2 days. The pattern of serum E₂ and progesterone levels in the periovulatory and luteal phase was not affected by the day of initiation of hMG therapy, although Group I patients demonstrated lower (P<0.05) E₂ levels on the 2 days prior to human chorionic gonadotropin (hCG) administration. In terms of follicle growth, Group II follicles consistently demonstrated a significantly (P<0.01,x ² test) larger proportion of medium- and large-sized follicles compared to Group I follicles on almost all of the days when ultrasonographic measurements were taken. In addition. Group II follicles demonstrated an earlier shift (day—1) to the larger follicles than Group I follicles (day 0). Significantly (P<0.001) more oocytes were recovered per uspirated follicle in Group II patients, but the fertilization rate per oocyte was greater (P<0.003) for Group I oocytes. Nevertheless, pregnancy rates did not differ between the two groups. It is suggested that a difference between the two groups of patients in the quantity or quality of gonadotropin receptor sites in the early part of the follicular phase may account for both the diminished E₂ production in the follicular phase and the persistent depressed follicular growth in Group I patients.     

Comparison of different follicle-stimulating hormone and luteinizing hormone ratios for ovulation induction during in vitro fertilization.

Five normally menstruating women were treated in an attempt to induce development of multiple follicles. They were randomly divided into two groups. The first group, consisting of three women, was treated with a combination of follicle stimulating hormone (FSH) and human menopausal gonadotropin (hMG) (combination FSH/hMG). The second group, two women, was treated with hMG only. Following a nonconceptual cycle, the treatments were exchanged. The increment patterns of serum estradiol during the follicular phase and progesterone levels in both groups were identical. Ultrasonographic scanning revealed similar number and size of the growing follicles, which subsequently terminated in the same oocyte recovery rate in both groups (7.6 +/- 3.4 oocytes/procedure in the combination FSH/hMG and 8.0 +/- 2.5 in the hMG-only group). Fertilization and cleavage rates were also similar. These data indicate that high FSH/LH levels in different ratios do not alter ovarian response and oocyte fertilization potential.     

A prospective comparative study on IVF outcomes with either purified FSH or human menopausal gonadotrophin in downregulated normogonadotrophic women

OBJECTIVE: In compare the use of purified follicle-stimulating hormone with that of a preparation containing follicle-stimulating hormone and luteinizing hormone in infertile females undergoing IVF. DESIGN: Open-labelled prospective controlled single-center study. SETTING: Nile Badrawy IVF unit. PARTICIPANTS: 153 infertile females undergoing their first cycle of IVF divided into 2 groups. Interventions: Ovarian stimulation was done with either highly purified FSH for group 1 (n = 75) or human menopausal gonadotrophin group 2 (n = 78) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound transvaginal oocyte retrieval followed by IVF and transfer of three embryos. OUTCOMES: Number of oocytes >18 mm at day of hCG, fertilization rate, embryo transfer rate, clinical pregnancy rate and incidence of ovarian hyperstimulation syndrome. RESULTS: The response to ovarian hyperstimulation was similar in both groups. The number of follicles >18 mm achieved at day of hCG was 12.3 +/- 0.9 (mean +/- SEM) following stimulation with 38.3 +/- 0.9 ampoules of Fostimon The Menogon-treated group needed 39.1 +/- 0.8 ampoules to produce 11.6 +/- 0.7 follicles. Fertilization rate (2PN/cell) was 58.6 vs. 64.2% in the Fostimon and Menogon group, respectively (p > 0.05). The number of embryos transferred per woman was 3.1 +/- 0.1 in the Fostimon group and 3.6 +/- 0.1 in the Menogon group. The pregnancy rate per woman was 33.3 vs. 25.6% in the Fostimon- and Menogon-treated groups, respectively (p > 0.05). Miscarriage rate was 16 vs 20%, respectively. However, the incidence of multiple pregnancies was significantly higher in the Fostimon-treated group (32%) vs. 10% only in the Menogon-treated group (p < 0.01). CONCLUSION: Purified FSH yields similar clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in a standard IVF regimen.     

A prospective randomized study of the optimum timing of human chorionic gonadotropin administration after pituitary desensitization in in vitro fertilization.

OBJECTIVE: To determine if there is an optimum time for the administration of human chorionic gonadotropin (hCG) after pituitary desensitization with gonadotropin-releasing hormone agonists (GnRH-a) has been achieved before ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Two hundred forty-seven patients undergoing an IVF treatment cycle who were randomly divided into three groups. INTERVENTIONS: All patients were administered subcutaneously buserelin acetate 500 micrograms/d from day 1 of the menstrual cycle. After pituitary desensitization had been achieved at least 14 days later, ovarian stimulation with human menopausal gonadotropin was commenced. Ovarian stimulation, cycle monitoring, oocyte recovery, and IVF and embryo transfer (ET) techniques were identical in all three groups. Patients in group 1 (n = 79) had hCG administered when the mean diameter of the largest follicle had reached 18 mm, at least two other follicles were greater than 14 mm, and serum estradiol (E2) levels were consistent with the number of follicles observed on ultrasound. Patients in groups 2 (n = 84) and 3 (n = 84) had hCG administered 1 day and 2 days, respectively, after the above criteria had been reached. RESULTS: The mean day of hCG administration (P less than 0.01), maximum serum E2 concentration (P = 0.06), number of days of serum E2 rise (P = 0.03), and mean diameter of the largest follicle (P less than 0.0001) were significantly different. There were, however, no significant differences in the mean number of preovulatory and medium size follicles, number of oocytes recovered or embryos transferred. There were also no significant differences in the oocyte recovery, fertilization and cleavage rates, in the number of embryos frozen, or in the pregnancy rates per initiated cycle and per ET. CONCLUSIONS: There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a.     

Treatment outcome in women with a single ovary versus patients with two ovaries undergoing in vitro fertilization and embryo transfer (IVF/ET)

OBJECTIVE: To compare ovarian response and pregnancy rate between women with one and two ovaries undergoing in vitro fertilization and embryo transfer (IVF/ET). STUDY DESIGN: 20 IVF/ET treatment cycles in ten women with a single ovary were compared with 60 IVF/ET cycles in 47 women with two ovaries. Both groups were matched for age and treated for mechanical infertility. In both groups treatment protocol included gonadotropin releasing hormone/human menopausal gonadotropin/human chorionic gonadotropin (GnRH/hMG/hCG). RESULTS: Effective daily dose of gonadotropins (3.7+/-0.7 vs. 3.6+/-1.0), mean 17beta-estradiol levels on day of hCG administration (1136+/-467 vs. 1343+/-776), number of retrieved oocytes (6.4+/-3.7 vs. 8.3+/-4.2) and number of embryos per transfer (3.0+/-0.7 vs 2.9+/-1.2) were not statistically different between the groups. A significantly higher pregnancy rate was observed among women with one ovary (52.9%) as compared with those with two ovaries (20.8%), (P=0.015). Multivariate logistic regression analysis demonstrated an odds ratio of 5.73 for patients with a single ovary. CONCLUSION: Treatment outcome in patients with a single ovary undergoing IVF/ET is comparable to those with two ovaries. The unexpected significantly higher pregnancy rate observed among these patients need to be further evaluated.     

The administration of glucocorticoids for the prevention of ovarian hyperstimulation syndrome in in vitro fertilization: a prospective randomized study.

OBJECTIVE: To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG). INTERVENTIONS: Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d. RESULTS: The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids. CONCLUSIONS: Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF.     

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.

OBJECTIVE: 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. DESIGN: Prospective randomized study. PATIENTS: Ninety-one patients having their first attempt at IVF. INTERVENTIONS: 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. RESULTS: 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. CONCLUSIONS: 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.     

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.