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Objective: To compare two gonadotropin-releasing hormone agonists (GnRH-a), buserelin acetate and leuprolide acetate [LA], used in combination with gonadotropins in ovarian stimulation for in vitro fertilization (IVF)., Design: Randomized prospective study., Setting: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona., Patients: Thirty-five pairs of IVF patients who were matched on age, indication, and number of attempts. These women were randomized to receive either buserelin acetate plus gonadotropins (group B) or LA plus gonadotropins (group L)., Main Outcome Measures: Luteolysis, ovarian response, and IVF outcome., Results: The mean time for total ovarian arrest and the total dose of gonadotropins and estradiol levels on the day of human chorionic gonadotropin administration were similar in the two groups of patients. The number of follicles punctured, the number of oocytes retrieved, and the percentage of mature oocytes in group L were significantly higher. The number of embryos suitable for replacement and cryopreservation was higher in group L compared with group B approaching statistical significance., Conclusion: Our results warrant further studies to compare different GnRH-a as therapeutic tools in IVF.

So far, the few studies performed on endometrial steroid receptors in in vitro fertilization (IVF) cycles have been carried out by the dextran-coated charcoal (DCC) method. Despite widespread efforts to standardize the DCC assay method, assay results still vary and thus, data obtained in IVF cycles are controversial. In the present article, late luteal estradiol (E2) and progesterone (P) receptor (R) levels were measured by a new monoclonal enzyme immunoassay (EIA) method in endometrial samples obtained from 21 patients in an IVF program who received no embryo transfer (ET) after ovarian stimulation with follicle-stimulating hormone/human menopausal gonadotrophin/human chorionic gonadotrophin under pituitary suppression with buserelin. Plasma levels of E2, P and prolactin (PRL) were measured in three blood samples collected in the midluteal phase. Results were compared with those obtained in a control group of 21 spontaneous cycles. E2, P and PRL were significantly higher in stimulated than in spontaneous cycles. The level of E2R was decreased in endometrium in IVF stimulated cycles, but PR remained unchanged.

Objective: To investigate the pathogenesis of the systemic hemodynamic disturbance and the renal production of vasodilator prostaglandins (PGs) in the ovarian hyperstimulation syndrome., Design: Prospective longitudinal study., Setting: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona., Patients: Five in vitro fertilization patients with ascites because of severe ovarian hyperstimulation syndrome., Main Outcome Measures: Measurement during the syndrome and 4 weeks after recovery of the following: cardiac output, arterial pressure, estimated peripheral vascular resistances, hematocrit, standard renal function tests, plasma renin activity, plasma aldosterone, norepinephrine and antidiuretic hormone concentrations, and urinary excretion of PGE2 and 6-keto-PGF1 alpha., Results: During the syndrome, all patients showed arterial hypotension (74.2 +/- 3.8 versus 85.8 +/- 1.0 mm Hg), tachycardia, increased cardiac output (6.4 +/- 0.2 versus 4.4 +/- 0.1 L/min), low peripheral vascular resistance (929 +/- 52 versus 1,568 +/- 51 dyn/sec per cm-5), high plasma levels of renin (72 +/- 25 versus 0.5 +/- 0.1 ng/mL per h-1), norepinephrine (639 +/- 141 versus 203 +/- 21 pg/mL) and antidiuretic hormone (6.1 +/- 1.6 versus 1.5 +/- 0.1 pg/mL), and increased urinary excretion of PGE2 (551 +/- 152 versus 106 +/- 44 pg/min) and 6-keto-PGF1 alpha (470 +/- 76 versus 99 +/- 11 pg/min). No evidence of hemoconcentration, as assessed by hematocrit, was observed in any patient., Conclusions: (1) Severe ovarian hyperstimulation syndrome is related to marked arteriolar vasodilation that leads to underfilling of the arterial vascular compartment and stimulation of endogenous vasoconstrictor systems and (2) the increased urinary excretion of PGs probably represents a homeostatic response to antagonize the renal effects of these systems.

Objective: To assess the prevalence of human immunodeficiency virus (HIV) antibody in infertility., Design: Prospective cross-sectional blind study., Setting: An infertility clinic in Barcelona., Patients: Three hundred thirty-five consecutive patients (308 infertile women and 27 spontaneous recurrent aborters) were seen between January 1989 and May 1990., Main Outcome Measure: Human immunodeficiency virus serostatus., Results: The rate of seropositivity in the group of patients studied was 0.3% (95% confidence interval 0% to 0.9%)., Conclusion: Further studies are desirable to establish the value of routine HIV testing in infertility patients as a population of women actively seeking pregnancy.

Fifteen infertile women with inadequate luteal phase, histologically documented in at least two separate cycles, and normal midluteal plasma levels of progesterone (greater than or equal to 10 ng/mL), estradiol (70 to 300 pg/mL), and prolactin (less than 20 ng/mL) received "pure" follicle-stimulating hormone (pFSH), 150 IU intramuscularly, for 4 days (days 1 to 4 of the cycle). The endometrial defect was corrected in 7 of the 15 (46.7%) patients during the first treated cycle. Hormonal levels were similar in control and treatment cycles. Two of 5 patients with no additional infertility factors except luteal phase deficiency (LPD) became pregnant and carried to term singleton pregnancies. In 5 additional infertile patients with normal luteal function as assessed by endometrial histological study (2 cycles) and hormone measurements (first study cycle), a third biopsy was performed in a consecutive cycle under pFSH administration. In no case was the normal secretory pattern impaired. It is concluded that (1) some forms of LPD may be successfully treated by early follicular pFSH therapy and (2) pFSH does not alter the normal endometrial secretory pattern.

Endometrial data, plasma progesterone levels and the outcome of pregnancy were analyzed in 22 infertility patients from whom endometrial biopsies had been inadvertently taken in early pregnancy. We found 22.7% (5 cases) of defective endometria in association with normal plasma progesterone levels (available in four patients). Daily plasma progesterone during the first 21st postovulatory days in the cycle of conception is reported in one of our patients. Fourteen of the 22 women delivered normal infants at term, 1 woman had a hydatidiform mole and 7 women aborted (31.8%). The relevance of endometrial biopsy in the cycle of conception and its influence on the outcome of pregnancy are discussed.

Fifty women with 2 or more previous first-trimester abortions and 300 infertile patients underwent a luteal phase evaluation by basal body temperature, plasma progesterone, estradiol and prolactin determination, and endometrial biopsy (repeated in a later cycle when the first was defective). An endometrial luteal phase deficiency was detected in 15 (30%) of aborting patients. In 13 (26%) of these women the endometrial defect was associated to normal hormonal levels. This condition was only present in 36 (12%) of the infertility cases (P less than 0.01). We conclude that the possible etiologic role of luteal phase defects in repeated abortion, is by a secretory insufficiency in the endometrial pattern despite normal plasma hormonal levels.

The presence of anti-DR antibodies with lymphocyte cytotoxicity test was studied in five groups of patients: 50 males with no history of blood transfusions who comprised the control group, 44 contraceptive-using women, 55 pregnant women, 41 primary sterile and 47 infertile patients. The high and similar degree of sensitization found in both pregnant and sterile patients lead us to the conclusion that anti-DR antibodies are not a cause of sterility and that spermatozoa are highly immunogenic. The biological significance of the antibodies is discussed.

This study was undertaken to examine the endometrial data in 200 infertile women whose three progesterone estimations per cycle totaled over 15 ng/ml when taken from 11 to 4 days preceding menstruation. Forty-three patients (21.5%) showed defective endometria in two separate cycles. No difference was found when plasma progesterone concentrations in this group were compared with those of the remaining 157 infertile patients with normal endometria. Further, plasma progesterone in infertile women (both groups) was similar to a control group of 12 fertile women with normal secretory endometria. Endometrial biopsy is essential in the evaluation of luteal function in infertility and cannot be totally replaced by the use of plasma progesterone in three samples during the luteal phase since it failed to detect as much as 21.5% of abnormal secretory phases.

The luteal function of 27 patients with mild endometriosis and infertility was compared with that of 50 infertile patients without endometriosis. The incidence of endometrial luteal phase deficiency was similar in both groups of patients. Luteal phase length and plasma levels of progesterone (P), estradiol (E2) and prolactin (PRL) in infertile patients (both groups) were similar to those in a group of 10 fertile women. We conclude that luteal phase defects should not be considered as a primary cause of infertility in mild endometriosis.

Two hundred seventy-four infertile patients and 43 women with two or more previous first-trimester abortions underwent a luteal function evaluation by basal body temperature, plasma progesterone, estradiol and prolactin determination, and endometrial biopsy (repeated in a later cycle when the first was defective). An endometrial luteal phase deficiency was detected in 37 (13.5%) of the infertility cases and in 14 (32.5%) of the patients with recurrent miscarriage. However, the endometrial defect was associated with normal hormonal levels in the great majority of patients (86.3%).

Thirty-three infertile patients presenting spontaneous ovulatory cycles with long follicular phases (greater than or equal to 20 days) underwent a luteal function evaluation by basal body temperature, plasma progesterone (P), estradiol, and prolactin determination, and endometrial biopsy study. An endometrial luteal phase deficiency (LPD) was detected in 13 patients (39.4%), although in 10 of them (77%) P levels were normal. This study shows a high incidence of endometrial LPD among cycles with delayed ovulation and that in cases of LPD related to abnormal folliculogenesis, the endometrium is a better indicator than plasma P.

We studied endometrial luteal phase in specimens from 660 biopsies done in 300 patients from our infertility clinic. A minimum of two (240 women) or three (60 women) endometrial biopsy specimens from separate cycles were taken regardless of the previous histologic findings in all patients. Statistical analysis of results by the McNemar and the Cochran Q tests for the significance of changes leads us to conclude that a minimum of two, and even three, endometrial biopsy specimens are needed for diagnosis of luteal phase deficiency.

Forty-four infertile patients with inadequate luteal phase histologically documented in at least two separate cycles and normal plasma levels of progesterone (P), estradiol (E2), and prolactin (PRL) were entered into treatment plans on a random basis involving at least 3 months of each of the following: P vaginal suppositories, dehydrogesterone, and no treatment. Success rates were similar for P (62.5%) and dehydrogesterone (68.7%), based on a corrected endometrial defect during the fourth treated cycle or when a term pregnancy was achieved. However, these figures are significantly different (P less than 0.001) when compared with 16.6% of the control group. In ten additional infertile patients with normal luteal function as assessed by endometrial histologic study and hormone measurements, a second biopsy was performed in a consecutive cycle under dehydrogesterone administration. In no case was the normal secretory pattern impaired. It is concluded that (1) both P and dehydrogesterone can be used to advantage in the treatment of luteal phase defects, and (2) therapy with dehydrogesterone does not alter the normal pattern of endometrial secretion.

We report here our series of seven patients treated for cervical infertility with combined high-dose conjugated estrogen and human menopausal gonadotropins. Nine of 11 treatment cycles (81.8%) were ovulatory, and 57.1% of treated patients conceived (three single pregnancies and one set of quadruplets). Criteria for selection of patients for this combined therapy are established.

To investigate the effect of maternal HLA antibodies on the evolution of pregnancy, we tested sera from 187 pregnant women for the presence of lymphocytotoxic antibodies (anti-HLA-A, -B, and -C and anti-B lymphocytes or anti-HLA-DR). Patients were studied before 20 weeks, between 21 and 30 weeks, and between 31 and 40 weeks' gestation. No correlation was found between the presence of such antibodies and obstetric complications, fetal wastage, placental weight, or infant birth weight. Patients with anti-DR antibodies delivered more female than male infants by a 3:1 ratio.

Hyperprolactinemia was detected in 15 of 130 infertile patients (11.5%) with regular menstrual cycles and no galactorrhea who underwent luteal phase evaluation by basal body temperature (BBT), plasma estradiol (E2), and progesterone (P) determination, and endometrial biopsy (repeated in a later cycle when the first was defective). Luteal phase length and plasma levels of P and E2 were similar in the hyperprolactinemic and normoprolactinemic patients. Moreover, a significantly higher incidence of inadequate luteal phase, histologically documented, was found in the normoprolactinemic group. It is concluded that the usefulness of plasma prolactin (PRL) determination in the evaluation of luteal function in infertility is scanty and that most histologically documented cases of luteal phase defects occur with euprolactinemia.

The effect of dehydrogesterone upon corpus luteum function as reflected by plasma progesterone levels was investigated in eight healthy women. No significant difference was found between control cycles and treated cycles when dehydrogesterone, 20 mg daily, was given orally for 10 days after ovulation.

Ten couples with a history of at least three (mean 3.8) consecutive spontaneous abortions of unknown etiology and 57 normal fertile couples (means 2.6 children) were tested for HLA antigens. The frequencies of shared HLA-A, -B and -DR antigens among members of the couples were similar in both groups. Our results, as well as analysis of the data in the literature, contradict HLA antigens sharing between parents as a determinant of recurrent spontaneous abortion.

Twenty infertile patients being treated with clomiphene citrate (CC) and human chorionic gonadotropin (hCG) for induction of ovulation, with a defective endometrial secretory pattern despite normal plasma levels of progesterone, estradiol, and prolactin, were entered into treatment plans on a random basis involving the following: CC-hCG plus dehydrogesterone (group 1), and CC-hCG (group 2). Success rates were similar in both groups (20% and 30%, respectively), based on a corrected endometrial defect during the second treated cycle. It is concluded that progestational agents are of low therapeutic value in endometrial luteal phase deficiency induced by CC.

Basal body temperature profiles, serial serum progesterone levels, and serial endometrial biopsies were studied in 15 infertile women during 21 ovulatory cycles. Ten cycles (in 9 women) demonstrated luteal phase defects (LPD), diagnosed by a histological lag in endometrial maturation, normal luteal phase length, and normal luteal phase serum progesterone levels. Both normal and LPD cycles had a maximum amount of endometrial cytosolic progesterone receptor (PgR) on days 13-15, with a significant decline thereafter. LPD cycles had significantly lower endometrial nuclear PgR concentrations than did normal cycles during the proliferative phase, but luteal phase endometrial nuclear PgR levels were similar in both groups. In 2 LPD women treated with dydrogesterone, normal endometrial maturation and a decline in endometrial cytosolic PgR concentrations in the late luteal phase were found. Therefore, with the exception of endometrial nuclear PgR concentrations during the proliferative phase, we found no evidence for a major abnormality in endometrial PgR levels in LPD cycles with a lag in endometrial histology.

Fifty infertile patients treated with clomiphene and hCG for induction of ovulation were studied with plasma progesterone measurement and endometrial histology. Five patients (10%) presented defective endometria and low plasma progesterone in spite of biphasic BBT charts with normal luteal phase length. Forty-five patients (90%) had significantly higher plasma progesterone concentrations than those found in a control group of fertile women, but a defective endometrial secretory pattern occurred in 19 of these 45 patients (42.3%). These data suggest the need for monitoring the response to clomiphene by endometrial histology in addition to BBT and plasma progesterone, or for supplemental therapy to overcome the endometrial luteal phase deficiency in clomiphene-treated cycles.