Minimal endometriosis and intrauterine insemination: does controlled ovarian hyperstimulation improve pregnancy rates?

Fifty normally menstruating women staged laparoscopically as having minimal endometriosis were given an option to be treated with intrauterine insemination with or without ovarian stimulation. Twenty-five patients had unmedicated natural cycles (ie, no medication for follicular stimulation), and 25 underwent controlled ovarian hyperstimulation. All subjects received hCG to time ovulation, followed 36 hours later with intrauterine insemination. Sixteen pregnancies, eight in each group, resulted from a total of 132 cycles. The cumulative probabilities of conception for the first, second, and third cycles were 0.13, 0.26, and 0.38 in the natural-cycles group and 0.12, 0.25, and 0.34 in the medicated-cycles group, respectively (P greater than .05). Monthly fecundity was 0.14 for the natural-cycles group and 0.13 for the medicated-cycles group (P greater than .05). We conclude that there is no difference in pregnancy rates or monthly fecundity over a 3-month period with controlled ovarian hyperstimulation as opposed to natural cycles combined with intrauterine insemination.     

Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To investigate the effectiveness of double IUI and to determine the optimal timing of IUI in relation to hCG administration. DESIGN: Prospective randomized study. SETTING: Infertility Center, Department of Obstetrics and Gynecology, University of Milan. PATIENT(S): Patients with male factor and unexplained infertility undergoing controlled ovarian hyperstimulation (COH) and IUI. INTERVENTION(S): After COH with clomiphene citrate and gonadotropins, patients were randomly assigned to one of the following groups: group A received a single IUI 34 hours after hCG administration, group B received a double IUI 12 hours and 34 hours after hCG administration, and group C received a double IUI 34 hours and 60 hours after hCG administration. MAIN OUTCOME MEASURE(S): Number of follicles > 15 mm in diameter on the day of hCG administration, number of motile spermatozoa inseminated, clinical pregnancy rate. RESULT(S): Two hundred seventy-three patients underwent 449 treatment cycles: 90 patients were treated for 156 cycles in group A, 92 patients for 144 cycles in group B, and 91 patients for 149 cycles in group C. The overall pregnancies rates for groups A, B, and C were 13 (14.4% per patient and 8.3% per cycle), 28 (30.4% per patient and 19.4% per cycle), and 10 (10.9% per patient and 6.7% per cycle), respectively. There was a statistically significant difference between group B and groups A and C. CONCLUSION(S): Our data indicate that two IUIs performed 12 hours and 34 hours after hCG administration is the most cost-effective regimen for women undergoing COH cycles with clomiphene citrate and gonadotropins. Although the second insemination adds up to a slightly higher cost, it significantly increases the chance of pregnancy.     

Cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination. Influence of the number of mature follicles at hCG administration

OBJECTIVE: To determine if cycle fecundity in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI) cycles is influenced by the number of mature follicles at the time of hCG administration. STUDY DESIGN: Retrospective data analysis of 75 infertility patients undergoing 164 consecutive COH/IUI cycles with FSH and/or hMG in a university-affiliated private infertility center. Cycles were compared for number of mature follicles (> or = 15 mm) and peak serum estradiol levels, total number of ampules and days of gonadotropin use, and clinical pregnancy rate. RESULTS: There was a statistically significant increase in cycle fecundity when three to four mature follicles were stimulated. Peak estradiol levels were significantly different in the groups, as predicted from the number of follicles. The groups were not statistically different in age or etiology of infertility. Group A (1-2 mature follicles) required significantly more FSH/hMG than group B (3-4 follicles) or group C (> or = 5 follicles). CONCLUSION: In COH/IUI cycles, three to four mature follicles yield improved cycle fecundity as compared to that in cycles with a smaller or larger number of follicles. These findings may help identify patients who will be more successful in conceiving with COH/IUI versus those who should be counseled to use other assisted reproductive technologies.     

Abnormal sperm morphology is highly predictive of pregnancy outcome during controlled ovarian hyperstimulation and intrauterine insemination

Purpose: The purpose of this study was to assess the predictive value of a modified form of Kruger's strict criteria for sperm morphology for pregnancy outcomes after intrauterine insemination (IUI) and controlled ovarian hyperstimulation (COH) in the presence of normal sperm concentration and motility. Materials and Methods: A retrospective review of 42 couples undergoing COH/IUI was stratified by favorable or unfavorable sperm morphology. End points were pregnancy or failure of treatment as defined by four or more cycles of COH/IUI without pregnancy. Results: An unfavorable morphology (<4%) was highly predictive of failure during COH-IUI (94.45%; 17/18). A normal PIF was a sensitive indicator of those patients who became pregnant (93.8%; 15/16) and had a fair specificity for failure to achieve pregnancy after four cycles of treatment (65.4%; 17/26). Couples with a favorable sperm morphology were 28.3 times as likely to achieve a pregnancy within four cycles of treatment as those with unfavorable sperm morphology [95% confidence limits, 3.2 to 250.5; P<0.001]. Conclusions: Abnormal strict morphologic assessment is both sensitive and specific for pregnancy outcomes in couples undergoing COH/IUI. Couples with persistently unfavorable sperm morphology should be counseled appropriately and would be better served by more aggressive treatment with in vitro fertilization and embryo transfer.Presented at the 51st Annual Meeting of the American Society for Reproductive Medicine, October 7–12, 1995, Seattle, Washington.     

Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination cycles

OBJECTIVE: This study was undertaken to determine the feasibility of administering human menopausal gonadotropin subcutaneously for controlled ovarian hyperstimulation with intrauterine insemination. Study Design: This was a prospective nonrandomized matched-group comparison. Study patients (n = 25) undergoing controlled ovarian hyperstimulation with intrauterine insemination infertility treatment between June 1998 and March 1999 self-administered human menopausal gonadotropin subcutaneously for ovulation induction. Cycles (n = 39) were analyzed for duration of human menopausal gonadotropin treatment, total number of ampules of human menopausal gonadotropin used, peak serum estradiol level, number of mature follicles (> or =15 mm), cycle fecundity, and acceptability of the subcutaneous route of human menopausal gonadotropin administration. Age-matched historical control subjects who followed the same protocol except for the route of human menopausal gonadotropin administration, which was instead intramuscular, were used for comparison. RESULTS: Study and control cycles did not differ with respect to duration of human menopausal gonadotropin treatment (7.49 vs 8.18 d), total number of ampules of human menopausal gonadotropin used (17.44 vs 19.55), peak serum estradiol level (881 vs 769 pg/mL), number of mature follicles (>/=15 mm; 3.39 vs 2.92), or cycle fecundity rate (15.4% vs 17.9%). Two study patients were switched from subcutaneous to intramuscular administration because of minor local injection site reactions. CONCLUSION: Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination treatment cycles was generally well tolerated and yielded stimulation parameters and pregnancy rates similar to those associated with the intramuscular route. Patients subjectively preferred subcutaneous human menopausal gonadotropin administration because of the ability to self-administer the injections, the use of a smaller injection needle, and reduced muscular pain at the injection site.     

Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women

Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.     

Gonadotropin-releasing hormone agonist improves the efficiency of controlled ovarian hyperstimulation/intrauterine insemination

OBJECTIVE: Leuprolide acetate (LA) has improved the efficiency of human menopausal gonadotropins (hMG) in in vitro fertilization cycles. We hypothesized that the combination of LA/hMG/intrauterine insemination (IUI) would be more efficacious than hMG/IUI cycles. DESIGN: During an 18-month period, all patients completing either a hMG/IUI cycle (group I) or a LA/hMG/IUI cycle (group II) had the characteristics and outcomes of their stimulation cycles assessed. The groups were not prospectively randomized. SETTING: Referral center at a tertiary care hospital. PATIENTS: One hundred twenty three patients in group I completed 219 cycles, and 64 patients in group II completed 102 cycles. Twenty-eight of the patients who failed to conceive with hMG/IUI were advanced to group II. MAIN OUTCOME MEASURES: Pregnancy/IUI is compared between the two groups. RESULTS: Group II demonstrated significantly greater clinical pregnancy/IUI than group I (26.5% and 16.0%, respectively, P less than 0.05), as well as a higher live birth/IUI (21.6% and 12.8%, respectively, P less than 0.05). No difference was present in the rate of fetal wastage or multiple births. CONCLUSIONS: In our patients with recalcitrant infertility, the addition of a gonadotropin-releasing hormone agonist to hMG/IUI improved the pregnancy rate, without increasing the rate of multiple births or fetal wastage.     

A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN: A randomized, prospective trial. PARTICIPANTS: Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS: Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION: In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination.     

超排卵对宫腔内人工授精周期妊娠率的影响

目的分析超排卵对人工授精结局的影响，探讨超排卵对不同人群治疗的有效性。方法回顾性分析我院生殖科2000年3月-2007年12月期间女方有自发排卵的739个人工授精周期，比较不孕原因、女方年龄、有无子宫内膜异位症等因素下超排卵与自然周期妊娠率。结果739个人工授精周期中，超排卵周期233个，自然周期506个，妊娠率分别为21．6％和13．5％（P〈0.05），不孕因素中，宫颈因素为378个，男性因素为100个，盆腔输卵管因素44个，子宫内膜异位症85个，不明原因132个，其中宫颈因素和不明原因不孕周期超排卵周期妊娠率明显高于自然周期（22．40％，14．62％；27．03％，12．63％ P〈0.05）；男性因素、输卵管因素、子宫内膜异位症、女方年龄大于37岁周期，超排卵与自然周期妊娠率差异无显著性（P〉0.05）。超排卵周期中，氯米芬与促性腺素周期临床妊娠率无显著差异（P〉0.05）。结论因宫颈因素、不明原因不孕行人工授精夫妇超排卵周期妊娠率高，而男性因素、子宫内膜异位症、盆腔输卵管因素或年龄大于37岁妇女进行人工授精时慎重选择排卵诱导。     

Controlled ovarian hyperstimulation and intrauterine insemination for treatment of infertility

Empirical therapy for subfertility using assisted reproductive technologies recently has gained popularity; however, the cost-effectiveness of these therapies, compared with an untreated control group, has not been established. Similarly, there has been no comparative cost analysis of the utility of controlled ovarian hyperstimulation and IUI in the management of the same condition. Significant PRs in untreated couples with subfertility mandate the design and execution of controlled trials to ascertain the role of controlled ovarian hyperstimulation and IUI in infertility therapy. Various disorders of subfertility have been treated with controlled ovarian hyperstimulation and IUI. The rationale for this therapy is the increase in gamete density at the site of fertilization, as with GIFT and IVF when used for management of the same problems. The live birth rate per initiated cycle and risk of complications are similar to results recently reported for GIFT and IVF. The utility of controlled ovarian hyperstimulation and IUI still remains controversial. When the relatively low direct and indirect costs of controlled ovarian hyperstimulation and IUI are considered, acknowledging the lack of prospective, controlled studies, this procedure appears to be at least as cost-effective as GIFT and IVF.     

Risk factors for high-order multiple pregnancy and multiple birth after controlled ovarian hyperstimulation: results of 4,062 intrauterine insemination cycles

OBJECTIVE: To determine factors responsible for high-order multiple pregnancy (HOMP) and high-order multiple births when multiple cycles of controlled ovarian hyperstimulation-IUI (COH-IUI) are performed. DESIGN: Retrospective analysis. SETTING: Private infertility clinic. PATIENT(S): Women (n = 2,272) who underwent 4,067 consecutive COH-IUI cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): High-order multiple pregnancy rate, pregnancy rate (PR), and birth rate (PR) per cycle. RESULT(S): High-order multiple pregnancy was related to number of follicles of diameter > or = 10 mm, age, and treatment cycle. For age <32 years, HOMP was 6% for three to six follicles and 20% for seven or more follicles. For ages 32 to 37 years, HOMP was 5% for three to six follicles and 12% for seven or more follicles. In the first COH-IUI cycle, HOMP was 8% for three to six follicles and 15% for seven or more follicles. In the second cycle, HOMP did not occur unless there were more than six follicles. No HOMP occurred after the second cycle. Pregnancy rate did not increase significantly when there were more than four follicles. Continuing COH-IUI past the third cycle resulted in additional pregnancies in patients with one to eight follicles. CONCLUSION(S): High-order multiple pregnancy can be predicted by age and number of follicles of diameter > or = 10 mm. Controlled ovarian hyperstimulation is not necessary to achieve satisfactory overall pregnancy rates if ovulation induction is continued past the third cycle in low responders.     

Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination

More than 17,000 intrauterine insemination (lUI) cycles were analysed retrospectively with respect to outcome according to differing aetiologies of infertility. The quantity and motility of spermatozoa in the final preparation used for insemination had a positive effect on the outcome, as classically observed in the past. It was found that advanced maternal age had a negative effect on the pregnancy rate and was associated with increased miscarriage rate. More interestingly, an exactly parallel effect was found for paternal age. The impact of increased age on necrospermia and sperm DNA structure is discussed as a probable direct cause of this paternal effect.     

Controlled ovarian hyperstimulation in women with polycystic ovarian syndrome with or without intrauterine insemination

Objective: To evaluate the value of intrauterine insemination (IUI) in controlled ovarian hyperstimulation (COH) among couples with polycystic ovary syndrome (PCOS) and normal semen analysis. Design: Retrospective cohort study Setting: University teaching center. Patients: PCOS couples with normal semen analysis that underwent COH with IUI or timed intercourse (TIC). Intervention: COH with clomiphene citrate, letrozole or gonadotropins with or without IUI. Main outcome measures: Clinical pregnancy rates. Results: Of a total 265 cycles, 151 cycles were with IUI and 114 others with TIC. No significant difference was found in the overall pregnancy rates between the TIC group (17.5%) and the IUI group (16.6%). Analysis of pregnancy rates according to the type of COH treatments did not demonstrate the advantages of IUI over TIC. Conclusion: Compared to timed intercourse, IUI does not increase the pregnancy rate in couples with PCOS and normal semen analysis treated with COH.     

Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles

Objective:To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. Materials and methods:One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients’ files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. Results:The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=–0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=–0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles ≥18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles ≥18 mm and 24% with ≥4 follicles ≥18 mm. Conclusion: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level at the day of hCG administration in a controlled ovarian hyperstimulation cycle in non-andrologic and non-peritubal factor infertility; however, there is a clear trend towards higher pregnancy rates with higher number of follicles. Received: 8 December 2000 / Accepted: 19 February 2001