Intrauterine insemination with donor semen. An evaluation of prognostic factors based on a review of 1131 cycles

OBJECTIVE: To identify prognostic factors influencing the outcome of infertility treatment using intrauterine insemination with donor semen (IUI-D). DESIGN: Retrospective study of all patients undergoing IUI-D between August 1st, 1990 and July 31st, 1998. SETTING: University-affiliated infertility clinic. PATIENTS: Three hundred and five couples undergoing 1131 IUI-D treatment cycles. MAIN OUTCOME MEASURES: Type of hormonal treatment, number of follicles, length of follicular phase, endometrial pattern, female age, infertility diagnosis and semen quality related to clinical pregnancy rate, cumulative birth rate and multiple gestations. RESULTS: Throughout the nine year period the overall clinical pregnancy rate per cycle was 22.3%, with an increase from 12.9% in 1990 to 34.6% in 1998. The multiple birth rate was 20.6%. The birth rate per couple was 61.1% after a mean of 3.2 treatment cycles. The pregnancy rate was highest in the first treatment cycle and the cumulative birth rate rose only slightly after the sixth treatment cycle. The following parameters were positively and significantly correlated to a successful outcome of IUI-D: i) the first treatment cycle - compared to the following up to six treatment cycles; ii) number of mature follicles - more than one - at the time of insemination, however, with an unacceptable high rate of multiple pregnancies when more than 3 mature follicles were present; iii) time of insemination after the 12th day in the cycle; iv) insemination after ovulation has occurred and; v) female age under 30 years. CONCLUSIONS: IUI-D is a simple and inexpensive treatment giving acceptable pregnancy rates for up to six treatment cycles if at least 2 mature follicles have developed at the time of insemination, which implies that hormonal ovarian stimulation and induction of ovulation is used, and ovulation has occurred at the time of insemination, which ought to take place after cycle day (cd) 12 with at least two million motile spermatozoa.     

Homologous intrauterine insemination in controlled ovarian hyperstimulation cycles: a comparison among three different regimens

OBJECTIVE: The objective was to assess the efficacy of double intrauterine insemination (IUI) over a single periovulatory IUI in patients undergoing controlled ovarian hyperstimulation with low-dose recombinant follicle stimulating hormone (rFSH) combined with human chorionic gonadotropin (HCG). STUDY DESIGN: Ninety-four infertile women were randomly assigned to three groups; in group A (38 patients, 47 cycles) a single IUI was performed 36 h after HCG administration combined with timed intercourse the day of HCG administration; within group B (43 patients, 48 cycles) IUI alone was performed 36 h after HCG administration; in group C (39 patients, 43 cycles) a double IUI 12 and 36 h after HCG administration was performed. RESULTS: The mean age and the causes of infertility were similar between the three groups. The number of follicles greater than 15 mm on the day of HCG administration and the overall dose of rFSH required per cycle was not significantly different among the groups. The pregnancy rate (PR) per cycle and per patient was 14.9% and 18.4% in group A, 10.4% and 11.6% in group B, 20.9% and 23.1% in group C, respectively. There was no statistically significant difference in PR among the three groups. CONCLUSION: In rFSH/HCG cycles, two IUIs performed 12 and 36 h after HCG administration do not significantly improve pregnancy rates over a single insemination performed 36 h after HCG administration combined with or without timed intercourse the day of HCG administration.     

Effectiveness of GnRH antagonist in intrauterine insemination cycles

Objective

To evaluate the effectiveness of GnRH antagonists in women undergoing controlled ovarian stimulation and intrauterine insemination cycles (COS/IUI).

Study design

Randomized controlled trial. Recruited women were randomized into two groups: GnRH antagonist and control group. The primary outcomes were incidence of premature LH surge and clinical pregnancy rates.

Results

One hundred and forty-one consecutive women were included in the study, with 70 in the antagonist group and 71 in the control arm. The baseline clinical characteristics were similar in both groups. The incidence of premature LH surge and premature luteinization was lower in the antagonist group as compared to the control group (5% vs. 10.3%, P = 0.45 and 5% vs. 13.8, P = 0.31) but not statistically significant. The clinical pregnancy rates were lower in the antagonist group (2.8% vs. 10%, P = 0.12), which was also not statistically significant.

Conclusion

The addition of GnRH antagonist during controlled ovarian stimulation and intrauterine insemination cycles does not lead to improvement in clinical pregnancy rates.     

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.     

Predictive factors for pregnancy during the first four intrauterine insemination cycles using gonadotropin

Abstract

Purpose: Although a variety of factors have been reported as affecting pregnancy rates after intrauterine insemination (IUI), there have been conflicting results on prognostic factors. This study aimed to determine predictive factors for pregnancy in patients undergoing the first four IUI cycles.

Methods: A total of 348 IUI cycles using clomiphene citrate or letrozole combined with gonadotropin, or gonadotropin only were analyzed. Baseline clinical characteristics, variables related to ovulation induction and sperm parameters were compared between pregnant (n?=?54) and non-pregnant groups (n?=?294). Logistic regression analysis was performed to identify factors that could predict a pregnancy.

Results: The overall clinical pregnancy rate was 15.5% (54/348) per cycle and 30.0% (54/180) per couple. During the first four IUI cycles, logistic regression analysis revealed that woman who were 39 years or older (OR: 0.263, 95% CI: 0.076–0.906, p?=?0.034), longer duration of infertility (OR: 0.967, 95% CI: 0.942–0.993, p?=?0.012), endometriosis (versus unexplained infertility; OR: 0.177, 95% CI: 0.040–0.775, p?=?0.022) and endometrial thickness below 7?mm (OR: 0.114, 95% CI: 0.015–0.862, p?=?0.035) were unfavorable factors to predict clinical pregnancy.

Conclusions: Women with old age, longer duration of infertility, the presence of endometriosis or thin endometrium in the preovulatory phase may have unfavorable outcomes during the first four IUI cycles.     

Premature LH and progesterone rise in intrauterine insemination cycles: analysis of related factors

Premature LH and progesterone surges are associated with different factors and hormonal modulators. The aim of the present study was (i) to investigate the clinical and laboratory factors and (ii) to highlight the importance of different stimulation protocols in associated premature LH and progesterone surges in intrauterine insemination (IUI) cycles. The study involved a retrospective investigation of 75 patients undergoing IUI for infertility treatment (135 IUI cycles) between 1996 and 2000, with initial serum LH concentrations >10 mIU/ml during ovarian stimulation. Ultrasound characteristics, follicular sizes, serum oestradiol, progesterone and LH concentrations and ovarian stimulation protocols were measured. There was a wide range of oestradiol serum concentrations (93-2245 pg/ml) and follicular size (12-25 mm). In 49.6% of cycles, the dominant follicle was <16.5 mm. Patients with >2 follicles measuring <15 mm had higher oestradiol serum concentrations (P = 0.008). Multiple regression analyses revealed no association between these variables and premature LH/progesterone surge. In conclusion, LH/progesterone surges cannot be predicted utilizing clinical parameters normally employed, e.g. ultrasound serum oestradiol assay or ovarian stimulation protocol. Patients with follicles >14 mm or more and with high numbers of small follicles and high oestradiol are at risk of a spontaneous LH surge. These variables can be used to time the administration of GnRH antagonist administration until better predictive factors are demonstrated.     

Relationship of follicle number and other factors to fecundability and multiple pregnancy in clomiphene citrate-induced intrauterine insemination cycles.

OBJECTIVE: To determine characteristics associated with pregnancy and multiple gestation after clomiphene citrate (CC)-intrauterine insemination (IUI). DESIGN: Prospective study of all patients undergoing CC-IUI between January 1, 1983 and December 31, 1989. SETTING: Private fertility clinic. PATIENTS: Eight hundred forty-nine patients undergoing 1,974 cycles of CC-IUI. MAIN OUTCOME MEASURES: Relationship between number and size of preovulatory follicles, age, additional infertility diagnosis, medication, and initial semen quality to fecundity, birth, and multiple gestation. RESULTS: Uncorrected, per cycle fecundity was 7.2%. The number of follicles greater than or equal to 12 mm (r = 0.055, P less than 0.05) was and the number greater than or equal to 15, 18, and 21 mm was not correlated with fecundity. Endometriosis with (P = 0.013) or without (P less than 0.0005) tubal adhesions and tubal adhesions alone (P = 0.005), decreased fecundability by 50%. Initial semen quality did not affect fecundity, unless semen concentration was less than 5 x 10(6)/mL or motility was less than 20%. Multiple pregnancy was not associated with the dose of CC, use of human chorionic gonadotropin, or number of follicles. CONCLUSIONS: Multiple pregnancy was unrelated to follicle numbers or to CC dose. The highest birth rates after CC-IUI occurred when initial sperm concentration was greater than or equal to 5 x 10(6)/mL, motility was greater than or equal to 20%, and no endometriosis or adhesions were present.     

Infectious complications of intrauterine insemination: a case report and literature review.

Intrauterine insemination is commonly performed in the treatment of infertility. Infectious complications associated with intrauterine insemination are frequently cited, though rarely reported. A review of the literature yields only five reported cases of pelvic infections subsequent to intrauterine insemination (IUI), and only two of these show firm evidence of infection, with none presenting bacteriologic confirmation. We report a case of Escherichia coli septicemia subsequent to an IUI performed on a patient with a large adenomyoma. Of 147 patients treated with IUI at Georgetown University from November 1987 through March 1990, this was the only infectious complication. The incidence of infectious complications in our series is thus 0.0068 (6.8 per 1,000 women). A review of infectious complications in 38 reported series on intrauterine inseminations reveals five infections in 3,129 patients. With the addition of our series to the literature, the prevalence of infectious complications is 1.83 per 1,000 women undergoing IUI. The rates were not significantly altered by semen washing with antibiotics, or the administration of prophylactic antibiotics to the woman (P = .81). We conclude that (1) the infection rate following IUI is small, (2) many of the infections subsequent to insemination were not associated with intrauterine insemination, (3) most reported cases of infection fail to show evidence for the actual presence of infection, and (4) the prevalence is unaltered by the administration of prophylactic antibiotics or washing the semen sample with antibiotics.     

Assessing the risk of multiple gestation in gonadotropin intrauterine insemination cycles

OBJECTIVE: The purpose of this study was to analyze factors for their ability to predict multiple gestation in women who undergo controlled ovarian hyperstimulation with gonadotropins (follicle-stimulating hormone/human menopausal gonadotropin) and intrauterine insemination. STUDY DESIGN: This was a retrospective analysis of the clinical and laboratory variables that are associated with multiple gestation. Data for 6 variables in 678 cycles of gonadotropin/intrauterine insemination between 1990 and 1999 were analyzed with survival analysis, Cox regression analysis, and multiple logistic regression. RESULTS: There were 99 clinical pregnancies among 678 cycles (14.6% per cycle) in 306 women. Of the 14 women with multiple gestations (14.1% of pregnancies), 11 women had twins, 2 women had triplets, and 1 woman had quadruplets. Age, days of gonadotropin treatment, total dose of gonadotropin, and number of follicles that were >or=15 mm at the time of human chorionic gonadotropin administration were statistically significant predictors of multiple gestation in >or=1 of the statistical models. CONCLUSION: The risk of multiple gestation with controlled ovarian hyperstimulation/intrauterine insemination in this study was relatively low. In addition to age, several controllable variables that are associated with multiple gestation were identified.     

Homologous artificial insemination for oligoasthenospermia: a randomized controlled study comparing intracervical and intrauterine techniques

Homologous artificial insemination (AIH) is used to treat infertility caused by oligoasthenospermia, despite the lack of controlled studies confirming its benefit. This prospective randomized controlled trial was undertaken to determine whether intracervical (IC-AIH) or intrauterine (IU-AIH) homologous artificial insemination improves pregnancy rates in couples with infertility attributable to oligoasthenospermia alone. Twenty couples were randomized to receive IC-AIH or IU-AIH. Sixty-three insemination cycles were completed. During the same study period, 35 cycles with timed vaginal intercourse alone were assessed. Four pregnancies occurred, all following timed vaginal intercourse. No pregnancies resulted from IC-AIH or IU-AIH. This suggests that neither IC-AIH nor IU-AIH is of benefit when oligoasthenospermia is the cause of infertility. Pregnancies previously attributed to AIH may also have been conceived as a result of vaginal intercourse. This confounding effect on the results of AIH should always be considered.     

Effectiveness of stimulated menstrual cycles and Percoll sperm preparation in intrauterine insemination

To examine the usefulness of intrauterine insemination in women with various fertility factors, we retrospectively analyzed data from women treated during 1986 and 1987. Ninety-three patients underwent 1-11 cycles of single or double procedures, for a total of 423 inseminations in 263 treatment cycles. Twenty-six patients (28%) conceived, for a 10% total pregnancy rate per cycle, with 58% of the pregnancies resulting from double inseminations per cycle. An average of two treatment cycles was required to achieve pregnancy. Eight pregnancies (31%) occurred in spontaneous cycles, while 18 (69%) occurred in stimulated cycles. While clomiphene citrate therapy was useful in anovulatory patients, it was of no benefit in ovulatory patients being treated with intrauterine insemination. Human menopausal gonadotropin therapy was of benefit in both ovulatory and anovulatory patients when combined with intrauterine insemination. The live birth rate was higher (75%) in spontaneous cycles than in stimulated cycles (44%). Semen preparation was accomplished by sperm washing in 61% of the pregnancies and by Percoll preparation in 39%. The effectiveness of the discontinuous Percoll gradient for semen preparation for insemination was suggested by a pregnancy rate of 9% per cycle. While the mean sperm count in the pregnant group was 44 million, successful pregnancy was accomplished with a double insemination of 880,000 and 1.16 million rapidly progressive sperm in the first and second inseminate, respectively. The data confirm the important role of intrauterine insemination for the treatment of infertility.     

A randomized study of simultaneous hCG administration with intrauterine insemination in stimulated cycles

Objective(s)

To compare the clinical pregnancy rates between intrauterine insemination (IUI) simultaneously or 34–36 h following hCG injection in gonadotropin-stimulated IUI cycles.

Study design

Randomized, prospective, controlled, study conducted in a university infertility clinic. Of 923 infertile couples, 220 couples with unexplained infertility or mild male factor infertility were included to the study. Before ovarian stimulation patients were randomized into two groups: IUI at 34–36 h after hCG injection (group I) (n = 106) and IUI simultaneously with hCG administration (group II) (n = 98). The primary outcome was clinical pregnancy rates.

Results

There was no significant difference between the groups according to baseline patient and cycle characteristics. Clinical pregnancy rates were 9.4% and 12.2% in group I and group II, respectively (p = 0.523). Although group II had better outcomes there was no statistically significant difference in clinical pregnancy rates between the different timing methods: IUI simultaneously with hCG versus IUI at 34–36 h after hCG (odds ratio (OR) = 1.35, 95% CI 0.53–3.42).

Conclusion(s)

There is no difference in simultaneous use of hCG injection compared to cycles in which IUI is performed after 34–36 h following hCG injection. Prospective randomized trials with larger sample sizes or meta-analyses are required.