Pregnancy outcome after laparoscopic fimbrioplasty in nonocclusive distal tubal disease.

OBJECTIVE: To determine pregnancy rates (PR) after fimbrioplasty and salpingostomy in nonocclusive distal tubal disease. To evaluate the relative impact of various factors using contemporary statistical analysis. DESIGN: Prospective cohort. SETTING: Tertiary institutional infertility clinic. PATIENTS(S): Infertility patients. INTERVENTION(S): Fimbrioplasty and salpingostomy. MAIN OUTCOME MEASURE(S): Cumulative PR, monthly fecundity rates, monthly probability of pregnancy, crude PR, and cure rates. RESULTS(S): Thirty-five percent of patients conceived with a cure rate of 72.2%, monthly probability of pregnancy of 3.9%, and monthly fecundity rate of 3.9%. Cumulative PRs were 22%, 35%, and 58% at 6, 12, and 24 months, respectively. Pairwise comparisons (unilateral, bilateral, or either) failed to detect any statistical difference between the salpingostomy and fimbrioplasty groups. Salpingostomy patients initially may have a higher tendency to become pregnant but appear to lose that advantage after the first few months. When patients with tubo-ovarian adhesions are excluded from the analysis, patients who underwent a bilateral salpingostomy as their sole procedure had better outcome compared with those who only underwent bilateral fimbrioplasty. There was no significant association between pregnancy outcome and the presence of endometriosis, other infertility factors, or tubo-ovarian adhesions. The staging of adnexal adhesions and endometriosis did not predict pregnancy outcome. CONCLUSION(S): Laparoscopic fimbrioplasty and salpingostomy are clinically efficacious for the treatment of nonocclusive distal tubal disease. After accounting for statistical interactions of various factors among them, no particular association with pregnancy outcome could be identified. This illustrates the need for a revision of the classification of patients with distal tubal disease.

Pregnancy rates after operative endoscopic treatment of total (neosalpingostomy) or near total (salpingostomy) distal tubal occlusion.

OBJECTIVE: To determine the efficacy of the endoscopic treatment of complete distal tubal occlusion or moderate to severe tubal phimosis and to analyze outcome using contemporary statistical methodologies. DESIGN: Prospective cohort analysis. SETTING: Tertiary-care institution. PATIENTS: One hundred thirteen consecutive patients undergoing a neosalpingostomy or salpingostomy. INTERVENTIONS: KTP/532 laser (Laserscope, Santa Clara, CA) laparoscopy. Additional infertility factors were treated postoperatively. MAIN OUTCOME MEASURES: Crude pregnancy rate (PR), monthly fecundity rate, monthly probability of pregnancy, cure rate, and cumulative PRs. Outcome was compared on the basis of the surgical procedure performed. The impact of endometriosis as well as other fertility factors was analyzed. RESULTS: Twenty-three patients conceived yielding a crude PR of 20.4%, a monthly fecundity rate of 2.6%, a monthly probability of pregnancy of 6.4%, and a cure rate of 52.4%. There were six ectopic pregnancies (5.3%). A significant difference was found among the cumulative pregnancy curves. The cumulative pregnancy curve for unilateral salpingostomy differed significantly from that of unilateral neosalpingostomy. Patients with endometriosis and no other infertility factors had a significantly better cumulative pregnancy curve compared with patients without endometriosis or other factors as well as compared with patients with no endometriosis but with other infertility factors. Patients undergoing bilateral neosalpingostomy had a cure rate of 9.0% whereas patients undergoing bilateral salpingostomy had a cure rate of 34.2%. CONCLUSIONS: Operative endoscopy yields PRs that are comparable to those reported in the literature for laparotomy. The presence of complete bilateral distal tubal occlusion has a negative impact on outcome.

KTP/532 laser laparoscopy in the treatment of endometriosis-associated infertility.

OBJECTIVE: To determine the clinical effectiveness of the KTP/532 laser in treating endometriosis-associated infertility and to analyze the impact of additional infertility factors on outcome. DESIGN: Prospective cohort analysis of 74 consecutive patients followed up to 24 months after surgery. SETTING: Tertiary institutional infertility clinic. MAIN OUTCOME MEASURES: Cumulative pregnancy rates (PRs), monthly fecundity rates, monthly probability of pregnancy, crude PRs, and cure rates. RESULTS: Thirty-eight percent (28) of patients conceived with a mean +/- SE time to conception of 7.2 +/- 0.8 months. The cure rates were 74% for the total patient sample, 51% for stage I, 69% for stage II, and 64% for stage III disease. Patients who had a cervical factor (P = 0.05), who underwent intrauterine insemination (P = 0.03), who received human menopausal gonadotropin (P = 0.03), or who had additional infertility factors (P = 0.02) had significantly lower crude PRs. The presence of additional infertility factors (P less than 0.02) and intrafimbrial adhesions (P less than 0.01) had a significant impact on cure rates. In the absence of additional factors, 60% (12) of patients with stage I and II conceived. When additional factors were excluded, the overall cure rate was 80%. CONCLUSION: The results indicate that the KTP/532 laser is an effective tool for the treatment of endometriosis-related infertility. The high prevalence of subtle adhesions may lend further impetus to operative laparoscopy for stage I and II disease. Additional infertility factors may adversely affect outcome.

Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group.

The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients. Dysmenorrhea, pelvic pain, and pelvic tenderness all responded significantly to LA treatment in comparison with placebo. Menses were suppressed in all of the LA patients. Estradiol decreased significantly to menopausal levels in the LA group. There were small to moderate changes in a variety of laboratory parameters, but these were not clinically significant. The most common adverse event was vasodilatation, occurring significantly more frequently in the LA group. Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of pain symptoms.

The effect of endometriomas on in vitro fertilization outcome.

To determine the effect of ovarian endometriomas on in vitro fertilization (IVF) outcome, two groups of patients were studied. Group I consisted of seven patients with ovarian endometriomas and severe pelvic adhesions treated for a total of 12 cycles. Group II patients consisted of eight patients with hydrosalpinges and comparable pelvic adhesions treated for a total of 27 cycles. There were no differences in the number of days required for stimulation or in the serum estradiol levels attained between the two groups. Group I patients were noted to have significantly fewer preovulatory follicles (1.42 vs 3.33, P less than 0.005), cycles with fertilization (28 vs 84%, P less than 0.005), and embryos transferred (0.78 vs 2.56, P = 0.01) than Group II patients. Three pregnancies occurred in Group II, while there were no conceptions among Group I patients. This study suggests that the presence of an ovarian endometrioma(s) has an adverse effect on IVF outcome and suggests that patients with ovarian endometriomas should have them removed prior to undergoing IVF.

Periovulatory follicular fluid hormone levels in spontaneous human cycles.

We measured follicular fluid hormone levels in 48 normally cycling infertile women who underwent follicle puncture and oocyte retrieval during diagnostic laparoscopy at time-bracketed intervals after an endogenous LH surge. Follicular fluid LH, FSH, PRL, estrone (E1), estradiol (E2), progesterone (P), androstenedione (A), and testosterone (T) concentrations and P/E2 and A/E2 ratios were determined. Oocytes were classified as germinal vesicle (gv), metaphase I (mI), metaphase II (mII), or degenerating (dg). Follicular fluid (ff) hormone levels then were correlated with the stage of oocyte maturation. There were no differences in ff E1 or E2 levels at any stage of oocyte maturation, except that the mean ff E2 concentration was significantly (P less than 0.05) lower in ff containing dg oocytes [2,474 +/- 1,435 (+/- SE) nmol/L] than in those containing the other oocyte stages. The mean P levels were significantly (P less than 0.0001) higher in ff containing mI (48,781 +/- 10,240 nmol/L) and mII (41,801 +/- 11,098 nmol/L) oocytes than in ff containing gv oocytes (1371 +/- 696 nmol/L). The mean A level was highest (P less than 0.01) in dg-associated ff. Similarly, T was highest (P less than 0.05) in ff containing dg (52 +/- 14 nmol/L) oocytes than in ff containing mI (10.7 +/- 10.1 nmol/L) or mII (10.1 +/- 4 nmol/L) oocytes, and it was also elevated (P less than 0.05) in gv ff (72 +/- 33 nmol/L) compared to mII ff. The above differences also were reflected in the P/E2 ratio, which was significantly higher (P less than 0.05) in mI and mII ff, as well as in the A/E2 ratio, which was higher (P less than 0.05) in ff containing mI and mII oocytes compared to ff containing gv or dg oocytes. These data define the evolving changes in the microenvironment of the follicular fluid of preovulatory follicles of normally cycling women. They also provide reference points for analysis of ff obtained from women during stimulated cycles intended for in vitro fertilization.

A comparison of the effects of Buserelin versus danazol on plasma lipoproteins during treatment of pelvic endometriosis.

Twelve patients receiving Buserelin and seven patients receiving danazol for treatment of endometriosis were studied to assess the effect of medication on plasma lipoproteins. Danazol significantly lowered plasma HDL-C levels at 6 months of treatment. Total plasma cholesterol was elevated at 6 months of therapy in the Buserelin group. No effect by either drug on plasma triglycerides was seen.

Spectrophotometric absorbance of follicular fluid: a predictor of oocyte fertilizing capability.

Follicular fluid volume, scoring of the oocyte-cumulus-corona-complex (OCCC), and spectrophotometric absorbance of the follicular fluid were separately compared between a group of fertilized (n = 53) and unfertilized oocytes (n = 35). Scoring of the OCCC and follicular fluid volumes was not found to be statistically different between the two groups. Spectrophotometric analysis of the follicular fluid in the visible spectrum demonstrated two peaks of maximum absorbance at 415 nm and 455 nm. The group of oocytes that fertilized was associated with follicular fluids that had significantly higher absorbances at 415 nm and 455 nm. In conclusion, follicular fluid volume and scoring of the OCCC were poor predictors of fertilizing capability; however, spectrophotometric absorbance, particularly at 455 nm, was positively correlated with oocyte fertilization.

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 1 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 less than 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 less than 0.01, chi 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 less than 0.001) more oocytes were recovered per aspirated follicle in Group II patients, but the fertilization rate per oocyte was greater (P less than 0.003) for Group I oocytes. Nevertheless, pregnancy rates did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered follicular development in clomiphene citrate versus human menopausal gonadotropin-stimulated cycles for in vitro fertilization.

The pattern of periovulatory and luteal phase serum estradiol (E2) and progesterone (P) as well as follicular fluid (FF) E2, P, androgen, gonadotropin, and prolactin concentrations of eight women undergoing clomiphene citrate (CC)/human chorionic gonadotropin (hCG) stimulation and eight women undergoing human menopausal gonadotropin (hMG)/hCG stimulation of follicular development for the purpose of in vitro fertilization were compared. Ovulation was induced with either a 5-day course of CC (100 mg/day beginning on day 5 of the cycle) or an individualized hMG regimen, and laparoscopy was performed 36 hours after hCG administration. The length of the luteal phase was significantly longer (P less than 0.05) in the CC-treated group as compared with the hMG-treated group. The pattern of serum E2 levels differed significantly (P less than 0.01) in that E2 levels were lower in the early and midluteal phase in CC-stimulated cycles; in addition, a delayed second E2 peak was observed in the late luteal phase in these women. Serum P levels, however, were lower in the hMG-stimulated group. Analysis of FF hormone concentrations revealed significantly (P less than 0.05) higher concentrations of E2 and androsterone in the FF of hMG-treated patients. It is concluded that follicular development in CC-stimulated cycles differs markedly from that in hMG-stimulated cycles. These differences may reflect either an altered follicular maturational process or may represent a direct inhibitory effect of CC on follicular steroidogenesis.

17 beta-estradiol and progesterone production by human granulosa-luteal cells isolated from human menopausal gonadotropin-stimulated cycles for in vitro fertilization.

The production of 17 beta-estradiol and progesterone (Prog) by human granulosa-luteal cells obtained from 24 aspirated follicles of 11 women undergoing laparoscopy in an in vitro fertilization program was studied. Follicular growth was stimulated with an individualized human menopausal gonadotropin regimen begun on either day 1 (group I; n = 5) or day 3 (group II; n = 6) of the menstrual cycle, and laparoscopy was performed 36 h after hCG administration. Granulosa-luteal cells were cultured for 2 h in culture medium alone or in the presence of either pregnenolone (10(-7) M) or testosterone (10(-7) M). Aromatase activity was present in the granulosa-luteal cells, as evidenced by a significant (P less than 0.001) increase in E2 production in the presence of testosterone. The addition of pregnenolone did not augment Prog production. Granulosa-luteal cells derived from Group II patients produced significantly (P less than 0.001) more Prog than those derived from group I patients. In addition, group II granulosa-luteal cells associated with mature oocyte-coronacumulus complexes produced significantly (P less than 0.001) more Prog than those in group I. Fertilization and pregnancy correlated with Prog production, in that granulosa-luteal cells associated with oocytes that were fertilized produced significantly (P less than 0.001) less Prog than those associated with nonfertilized oocytes. Granulosa-luteal cells from the 2 patients in this series who conceived demonstrated a further significant (P less than 0.02) reduction in Prog production. It appears that administration of human menopausal gonadotropin early (day 1) in the follicular phase results in incomplete maturation of the granulosa cells. Furthermore, the optimal oocyte, in terms of successful fertilization, may be one derived from a follicle that has undergone appropriate stimulation resulting in adequate maturation, but has not surpassed that point.

Human chorionic gonadotropin and prolactin modulation of early luteal function and luteinizing hormone receptor-binding activity in cultured human granulosa-luteal cells.

These studies were undertaken to explore the roles of both hCG and PRL in the modulation of early luteal function in the human. Human granulosa-luteal cells isolated during cycles stimulated by human menopausal gonadotropin hCG were obtained at the time of follicle aspiration and cultured to determine the effects of hCG and PRL on both progesterone and hCG receptor binding. Progesterone production by hCG-stimulated granulosa-luteal cells was increased 3.5-fold over unstimulated levels after 120 h, with maximal stimulation at hCG concentrations greater than 1 IU/ml. [125I]hCG binding to granulosa luteal cells was increased 3-fold in cells cultured with hCG (10 IU/ml) after both 48 h (P less than 0.03) and 96 h (P less than 0.02) in culture. hCG (1 IU/ml) stimulated a significant increase in progesterone production above basal levels after 72 h of culture, which continued to increase until 96 h of culture; 20 alpha-dihydroprogesterone (20 alpha-OH progesterone) production also was increased by hCG (1 IU/ml) at 72 h of culture, but unlike progesterone production, showed no further increase. In both the presence and absence of hCG, granulosa-luteal cells cultured with PRL (100 ng/ml) produced significantly more 20 alpha-OH progesterone (P less than 0.04 and P less than 0.02, respectively) after several days than cells cultured without PRL. In addition, progesterone production in the presence of hCG (10 IU/ml) decreased significantly (P less than 0.04) as 20 alpha-OH progesterone levels increased. Equivalent amounts of [125I]hCG were bound by human granulosa-luteal cells cultured with and without PRL (100 ng/ml). These results show that cultured human granulosa-luteal cells are responsive to hCG, with parallel increases in both progesterone production and [125I]hCG receptor binding. The presence of PRL (100 ng/ml) had no effect on [125I]hCG binding. In both the presence and absence of hCG, PRL resulted in an increase in 20 alpha-OH progesterone production and, in the presence of hCG (10 IU/ml), a decrease in progesterone production after several days in culture.

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.

The periovulatory and luteal phase of conception cycles following in vitro fertilization and embryo transfer.

The pattern of periovulatory and luteal phase levels of serum estradiol (E2) and progesterone (P) were compared between 8 conception and 28 nonconception cycles of patients undergoing in vitro fertilization (IVF). Ten additional women served as control subjects and did not undergo follicular aspiration. Follicle growth was induced with an individualized Pergonal (human menopausal gonadotropin) regimen, and laparoscopy was performed 36 hours after human chorionic gonadotropin administration. The length of the luteal phase did not differ significantly among the three groups and was between 14 and 15 days in duration. When IVF conception cycles were compared with nonconception cycles, although no difference in the number of large follicles was observed (4.25 +/- 0.45 versus 3.6 +/- 0.25), the patterns of E2 and P differed significantly. Daily serum E2 levels tended to be higher in the periovulatory phase in conception cycles when compared with nonconception cycles, and were significantly (P less than 0.05) higher in the early, mid, and late luteal phases. Serum P levels were significantly higher (P less than 0.05) in conception cycles from the midluteal phase onward. A decline in both serum E2 and P in the midluteal phase in conception cycles suggested some degree of corpus luteum deficiency. It is suggested that high E2 levels in the periovulatory phase may be an indicator of better follicular development under human menopausal gonadotropin stimulation and that the deficiency observed in the late luteal phase is overcome with the establishment of pregnancy.

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 regimen was continued for another 1-3 days, depending on the individual's ovarian response (mean, 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 ova was recovered. The oocytes were pre-incubated for 8 or 24 hr, according to the morphological degree of mucification 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 pregnancy/transfer rate was 21%. Of the pregnant women 5 of 16 (31%) aborted between 6 and 10 weeks of gestation and 1 (6%) had an ectopic pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Pregnancy success following surgical correction of imperforate hymen and complete transverse vaginal septum.

Pregnancy success was evaluated in 48 women following surgical correction of a vaginal obstruction due to imperforate hymen (N = 22) or to a complete transverse vaginal septum (N = 26). Pregnancy success was more likely to occur following surgical correction of imperforate hymen (P less than .05). Patients with a complete transverse septum in the middle or upper vagina were less likely to conceive than were patients with a septum in the lower vagina. Prompt diagnosis and surgical correction to drain accumulated blood may preserve preserve fertility possibly through the prevention of endometriosis.