Intrauterine insemination-ready versus conventional semen cryopreservation for donor insemination: a comparison of retrospective results and a prospective, randomized trial.

OBJECTIVE: To compare fecundity rates following intrauterine insemination (IUI) with donor sperm frozen conventionally versus an IUI-ready preparation. DESIGN: Both retrospective results and a prospective, randomized study where recipients were assigned to one of two sperm cryopreservation methods in each cycle of intrauterine insemination are reported. SETTING: University-based infertility practice, affiliated private practices, and andrology laboratory. PATIENT(S): Women desiring therapeutic insemination in an effort to establish pregnancy. INTERVENTION(S): Intrauterine insemination with donor sperm frozen conventionally or by an IUI-ready protocol. MAIN OUTCOME MEASURE(S): Cycle fecundity in donor IUI recipients. RESULT(S): In a retrospective analysis involving 642 inseminations in 209 recipients, 79 pregnancies were recorded for an overall pregnancy rate of 12.3% per insemination (or cycle): 11.3% with IUI-ready sperm and 13.9% with conventionally preserved sperm. In a follow-up prospective, randomized study, the pregnancy rate for IUI-ready sperm preparations was 36% per cycle (14 of 39) whereas that for conventionally preserved sperm was 19.6% per cycle (9 of 46). Thirteen of the 23 pregnancies occurred in the first study cycle of insemination; only two pregnancies were observed in patients undergoing more than four cycles of insemination. CONCLUSION(S): Cycle fecundity for IUI-ready donor sperm is equivalent to conventional cryopreserved sperm based on both prospective and retrospective assessments.     

Optimization of artificial inseminations with donor semen: a four-year experience

OBJECTIVE: Our aim was to analyse the results of a donor insemination program using ovarian stimulation, swim-up sperm preparation and intrauterine insemination proposed to women with a maximum age of 39. Incidence of several clinical and biological parameters on success rates was investigated. PATIENTS AND METHODS: Retrospective analysis of the results of 249 cycles performed in 106 couples during a four-year period is reported. RESULTS: Overall pregnancy rate of 28.1% and delivery rate of 22% per cycle were achieved, with a multiple pregnancy rate of 11.4%. Most of the pregnancies (84%) were obtained before the fourth insemination. Among the different parameters studied the total number of motile sperm inseminated was found to be the most important factor for success rate: pregnancy rate per cycle reached 40.4% if more than 1.5 million progressive sperm were inseminated vs. 24.7% if they were less than 1.5 million (P<0.05). DISCUSSION AND CONCLUSION: In precise conditions, outcome of inseminations with donor semen can reach satisfying pregnancy rates, being a valuable help for couples suffering of long-time infertility.     

Life table analysis of intrauterine insemination pregnancy rates

One hundred twenty-eight couples undergoing intrauterine inseminations were retrospectively reviewed. Life table methodology was used to analyze cumulative pregnancy rates and monthly fecundability. Respective 6- and 12-month cumulative pregnancy rates for each diagnostic group receiving intrauterine insemination were: cervical factor, 28.6% and 42.8%; male factor, 16.7% and 16.7%; female immune factor, 66.7% and 100.0%; male immune factor, 37.5% and 68.8%; and empiric treatment, 60.0% and 60.0%. There was no difference in pregnancy rates between sperm processed with a swim-up in Ham's F-10 or a two-gradient Percoll system. Abnormal sperm penetration assay results in patients with male factor did significantly (p = 0.05) lower the pregnancy rate. It is concluded that if no pregnancy has occurred after six cycles of inseminations, further workup or other treatment may be initiated, but additional pregnancies can be achieved from the seventh through the twelfth cycles of intrauterine insemination.     

Retrograde ejaculation: successful treatment with artificial insemination.

Retrograde ejaculation is characterized by aspermia or oligospermia and results from an incompetent bladder neck, often due to a dysfunction of the internal sphincter. In almost 3 years, eight couples who suffered from infertility due to retrograde ejaculation were treated with inseminations with spermatozoa gained from the urine. Ovulation was predicted on the basis of blood LH levels. The urine-semen sample was collected in 100 mL of Hepes medium and 5 mL 1% human albumin (pH 7.4). After centrifuging, the remaining sperm pellet was dispersed on a Percoll gradient. After centrifuging and resuspending, followed by two washing procedures with Ham's F-10 and human albumin 1%, the remaining sample was used for intrauterine insemination. Twelve pregnancies were thus achieved; two women became pregnant twice and one three times. The pregnancy rate per cycle was 44.4%. In seven couples, pregnancy was achieved within three cycles. Four pregnancies ended in spontaneous abortion and five ended in the birth of a healthy child; three pregnancies were continuing at the time of writing. Retrograde ejaculation can be treated successfully with inseminations using spermatozoa obtained from urine. It seems important to collect the urine-semen sample in a buffered medium and to time the insemination on the basis of the LH surge.     

Artificial insemination: a comparison of pregnancy rates with intrauterine versus cervical insemination and washed sperm versus serum swim-up sperm preparations

A four-cycle artificial insemination protocol was undertaken, with luteinizing hormone (LH) timing, to compare washed sperm and serum swim-up sperm preparations and cervical and intrauterine insemination. Of the 75 patients entered into the protocol series, 63 finished all 4 cycles. During the treatment period, 24 patients became pregnant, 20 of whom were donor (AID) pregnancies (out of 52 patients) and 4 were husband (AIH) pregnancies (out of 11 patients). Seventy-five percent of the pregnancies were intrauterine, whereas only 25% were from cervical inseminations. Sixty-two percent of the pregnancies were due to serum swim-up sperm preparations, and 38% were due to washed sperm preparations. The data indicate substantially higher pregnancy rates can be obtained with intrauterine insemination and suggest that additional studies are necessary to determine if the method of sperm preparation significantly influences pregnancy rates.     

Intrauterine insemination: the University of Minnesota experience

Forty-five patients initiated intrauterine insemination between October 1981 and August 1983. Indications for insemination included poor semen (count less than 20 X 10(6)/ml and/or motility less than 40%), poor cervical mucus, presence of sperm antibodies, unexplained poor postcoital tests, or various combinations of the above. During this time period, 374 inseminations were performed in 163 cycles and resulted in eight pregnancies in the 45 patients receiving artificial insemination by homologous donor, for an overall pregnancy rate of 17.4%. The fact that five of the pregnancies occurred in the first insemination cycle and two in the second cycle was felt to indicate a cause-and-effect relationship. A trial of intrauterine insemination in selected patients would appear to be warranted.     

Análisis de los factores de influencia sobre el resultado de 500 ciclos de inseminación intrauterina homóloga

Objective

To evaluate the results and analyse different factors influencing pregnancy rate using homologous intrauterine insemination.

Subjects and methods

Retrospective analysis of 500 homologous intrauterine insemination cycles in 183 infertile couples. Only one insemination per stimulated ovarian cycle was performed in patients with: mild endometriosis, ovulatory factor, male subfertility or unexplained infertility. We studied female age, duration of infertility, stimulation protocol, number of cycle, number of preovulatory follicles, motile sperm count and endometrial thickness related to pregnancy rate.

Results

Pregnancy rate per couple was 24% and per intrauterine insemination 9%, 11% was multiple pregnancies. Best outcome has been got in women younger than 37 years (P=.048) and in cycles with more than one preovulatory follicle. Other studied factors did not have influence in homologous intrauterine insemination outcome.

Conclusions

Female age is a prognostic factor for homologous intrauterine insemination with poor outcome in women older than 38 years. Cycles with more than one preovolatory follicle have better outcome. No differences in pregnancy rate have been achieved with motile sperm count over 1.5 millions/0.3 ml.     

One artificial insemination per cycle with donor sperm is as efficacious as two inseminations

Purpose To compare pregnancy rates per treatment cycle of artificial inseminations with donor sperm in patients receiving one versus two inseminations.Methods Retrospective cross-sectioned analysis of 167 patients who underwent 869 cycles receiving one or two donor inseminations were reviewed from 1987 through 1993 at our institution.Results A total of 256 cycles with one donor insemination per cycle resulted in 21 pregnancies and a cycle of fecundity of 8.2%, and 613 cycles with two donor inseminations resulted in 35 pregnancies and a cycle fecundity of 5.7%. Life table and logistic cumulative probability analysis of pregnancy occurrence showed no difference between treatment groups.Conclusions These data suggest there are no important clinical differences of cycle fecundity or cure rate in one versus two inseminations with donor sperm. Economic costs of two inseminations may not be justified.Presented in part at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

A prospective study of intrauterine insemination of processed sperm from men with oligoasthenospermia in superovulated women

The effectiveness of intrauterine insemination (IUI) was compared with that of intracervical insemination (ICI) in 49 infertile couples, in whom the major cause for infertility was oligoasthenospermia. All women had ovulation stimulated with either a clomiphene citrate (CC)-human gonadotropin combination or human gonadotropins alone. The ovulatory dose of human chorionic gonadotropin (hCG) was given after adequate estradiol levels were reached. The timing of inseminations was standardized--IUI was 28 hours after hCG and ICI was immediately after hCG administration. Only one insemination per month was performed with either IUI or ICI. The first treatment cycle was assigned randomly to be either IUI or ICI, and subsequent inseminations were alternated. A total of 182 cycles were completed, with 96 IUIs and 86 ICIs. Pregnancy occurred in eight patients, seven with IUI (14.3%) and one with ICI (2.0%); the difference is significant at P less than 0.05. The pregnancy rate per treatment cycle was 7.3% versus 1.2% (P less than 0.001). This study supports the use of IUI with processed sperm in the treatment of infertility due to oligoasthenospermia.     

Predictors of success with the use of donor sperm

OBJECTIVE: This study was undertaken to assess the effect of multiple factors that influence the success rate and time to conception among couples undergoing donor sperm insemination. STUDY DESIGN: A retrospective analysis of 960 cycles of frozen donor sperm insemination was performed at the University of Florida. Cycle pregnancy rates and cumulative probability of pregnancy were compared using several variables. RESULTS: The pregnancy rate was 12.1% per treatment cycle, and the cumulative probability of pregnancy exceeded 80% for the entire cohort. Seventy percent of pregnancies resulted in a liveborn infant. Age had a profound impact on the cycle pregnancy rate. The cycle pregnancy rates for women younger than 30 years, between the ages of 30 and 35 years, between the ages of 35 and 40 years, and older than 40 years were 15.8%, 14.6%, 8.2%, and 0%, respectively. There was a trend toward higher cycle pregnancy rates in women with prior pregnancies versus women without prior pregnancies of 14.4% and 12.3%, respectively. Parity had no effect on the cycle pregnancy rate or the cumulative probability of pregnancy. There was a trend toward higher cumulative probability of pregnancy in women whose partners were azoospermic versus oligospermic. There was no difference in pregnancy rates obtained with the Percoll wash gradient versus the Isolate gradient. At >20 million total motile sperm per insemination, there was no threshold above which the pregnancy rate was improved. CONCLUSION: The most significant influence on pregnancy rates in the donor sperm insemination program at the University of Florida was maternal age. Nulligravidity and a diagnosis of mild oligospermia in the man may have a negative impact on pregnancy rates.     

Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles

OBJECTIVE: To identify prognostic factors influencing the outcome of infertility treatment using homologous intrauterine inseminations (IUI-H). DESIGN: Retrospective study of all patients undergoing IUI-H at the Fertility Clinic, Odense University Hospital from August 1st, 1990 to July 31st, 1998. SETTING: University-affiliated infertility clinic. PATIENTS: Eight hundred and ninety-three couples undergoing 2473 IUI-H treatment cycles. MAIN OUTCOME MEASURES: Infertility diagnosis, female age, number of follicles, type of hormonal treatment, length of follicular phase, endometrial pattern, 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 IUI-H cycle was 11.9% with a significant increase from 8.7% in 1990 to 14.8% in 1998. The multiple birth rate was 18.1%. The birth rate per couple was 27.2% after a mean of 2.8 treatment cycles. The pregnancy rate was highest in the first treatment cycle and the cumulative birth rate rose only slightly after the fourth treatment cycle. Of the main outcome measures the following were positively and significantly related to a successful outcome of IUI: i) The first treatment cycle - compared to the following up to six treatment cycles; ii) number of mature follicles up to five - at the time of insemination, however, with an unacceptable high rate of multiple pregnancies with more than 4 mature follicles; iii) use of CC/hMG-FSH as compared to CC only for ovarian stimulation; iv) number of motile sperms inseminated exceeding 5 million; v) time of insemination between the 13th and the 16th day in the cycle and vi) anovulatory or idiopathic infertility. CONCLUSIONS: IUI-H is a simple and inexpensive treatment giving acceptable pregnancy rates for up to four treatment cycles providing that at least 3 to 4 mature follicles have developed at the time of insemination, which implies that hormonal ovarian stimulation and induction of ovulation is used, that insemination occurs between cycle day 13 and 16 and that at least 5 million motile sperms are available for insemination. Our results indicate that in the presence of tubal pathology or less than 5 million motile sperms, the couples should be referred directly to IVF-treatment.     

Experience with intrauterine insemination for cervical factor and oligospermia

In the past 100 years, interest in intrauterine insemination for cervical factor has waxed and waned. Recently the advent of in vitro fertilization, with improved methods of sperm washing and preparation, has revived interest in intrauterine insemination as a modality for the treatment of infertility. Twenty-seven couples with infertility resulting from cervical factor and/or oligospermia were entered into our intrauterine insemination protocol. A total of 107 intrauterine inseminations were performed in 85 menstrual cycles. Nineteen couples with a cervical factor as the major factor in their infertility experienced three pregnancies (16%). The remaining eight couples who had oligospermia with or without cervical factor produced no pregnancies. No major complications occurred from this procedure. In view of the low pregnancy rate experienced in this study, we must seriously question the value of intrauterine insemination in the treatment of cervical factors and/or oligospermia.     

Delayed timing of intrauterine insemination results in a significantly improved pregnancy rate in female partners of quadriplegic men

Objective: To review pregnancy rates obtained with three protocols used during development of a successful therapy for infertility in couples in which the male partner had spinal cord injury.

Design: Retrospective chart review.

Setting: Private infertility center.

Patient(s): Eleven quadriplegic men and their spouses undergoing intrauterine insemination.

Intervention(s): Protocol 1: Intrauterine insemination was performed 24 hours after the LH surge was detected in unstimulated cycles. Sperm were prepared by standard sperm washing. Protocol 2: Female partners were stimulated with clomiphene citrate and hCG. Sperm were inseminated 32–34 hours after hCG injection. Sperm preparation was by serum swim-up or density gradient preparation. Protocol 3: Identical to protocol 2, except the insemination was delayed to 38–40 hours after hCG injection.

Main Outcome Measure(s): Pregnancy rates.

Result(s): Five patients were enrolled into protocol 1 and underwent a total of 19 inseminations with no subsequent pregnancies. They then underwent protocol 2, but no pregnancies resulted from inseminations. Four of the original couples, along with six additional couples, underwent insemination in protocol 3. A total of 19 inseminations were performed, and 6 of the 10 patients (60%) became pregnant. The success of insemination at 38–40 hours after hCG administration was significantly better than that of the initial two protocols (P<.05). No differences were observed in sperm quality between protocol 2 and protocol 3. Overall, 73% (8 of 11) of the patients became pregnant.

Conclusion(s): Intrauterine insemination 38-40 hours after the hCG injection results in an improved chance of pregnancy. These results indicate that many couples with spinal cord injury-associated male infertility can be treated with intrauterine insemination of sperm treated by serum swim-up, with a high probability of success.     

Intrauterine insemination of cryopreserved donor semen

The use of cryopreserved specimens is becoming the standard of care for donor insemination. Commercial specimens often have low numbers of actively motile sperm. Intrauterine insemination may be of value in the wives of men with oligoasthenospermia. Accordingly, an intrauterine insemination protocol using one or two vials of commercial semen with a minimum of 24 million motile sperm per vial was used to determine if acceptable monthly conception rates could be obtained. During the study period, there were 82 insemination cycles, resulting in 20 pregnancies in 35 women. The monthly conception rate was 24% and monthly ongoing pregnancy rate was 18%. If confirmed by other investigators, intrauterine insemination may be a way to improve the pregnancy rate with cryopreserved semen.     

Comparison of fecundability with fresh and frozen semen in therapeutic donor insemination

A series of 401 therapeutic donor insemination (TDI) cycles was analyzed for determining the effect on fecundability of fresh versus cryopreserved semen, the number of inseminations per cycle, recipient age, and the reproductive health of the TDI recipient. We followed a protocol in which inseminations were performed during the periovulatory period determined by urinary luteinizing hormone surge or ultrasound-timed human chorionic gonadotropin injection. The minimum standard for insemination with fresh or cryopreserved semen was a total of 40 X 10(6) grade 3 sperm. We found no decreased fecundability when using frozen semen, rather than freshly ejaculated specimens. The number of inseminations per cycle did not affect the pregnancy outcome after TDI. The reproductive health of the recipient had a significant effect on the pregnancy rate. Fecundability was 15.6% for healthy women, as compared with 6.7% for women with a diagnosis of moderate, severe, or extensive endometriosis, pelvic adhesions, tubal disease, or ovulatory dysfunction. To avoid transmission of human T-lymphotropic virus type III from sperm donor to TDI recipient, we have recently utilized an exclusively frozen TDI program. With well-timed inseminations of 40 X 10(6) grade 3 motile sperm, we have been able to attain pregnancy rates similar to those previously obtained with fresh samples.     

A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm

Cryopreserved sperm have lowered fertility when compared with fresh sperm in artificial insemination by donor programs. The purpose of this study was to compare pregnancy rates following intrauterine insemination (IUI) and intracervical insemination (ICI) with cryopreserved sperm in a prospective trial using the patient as her own control. A total of 154 patients were randomized into alternating treatment cycles and underwent 238 cycles of IUI and 229 cycles of ICI. The pregnancy rate per treatment cycle was 9.7% following IUI and 3.9% following ICI. Treatment outcome was influenced by patient age, ovulatory status, and endometriosis. Pregnancy success correlated well with the post-thaw survival of sperm and the number of motile cells inseminated. In spite of having normal semen parameters, some donors were found to have markedly reduced sperm fecundity. We conclude that IUI with cryopreserved sperm can be an effective treatment for couples with infertility, genetic indications, or other reasons.     

One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature

OBJECTIVE: To study the efficacy of performing two inseminations per cycle in IUI with husband's sperm compared with one insemination per cycle. DESIGN: Meta-analysis. SETTING: Randomized and prospective trials comparing two inseminations vs. one insemination per cycle in IUI with husband's sperm, retrieved by MEDLINE and Cochrane Library searches (1966-2001) and a manual search of the abstracts of the European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine annual meetings (1990-2001). PATIENT(S): A total of 865 patients underwent 1156 cycles of IUI with husband's sperm. INTERVENTION(S): After different ovarian stimulation protocols, one or two inseminations were performed. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle. Detected studies were tested for homogeneity. Because heterogeneity was observed, DerSimonian-Laird relative risk with alleatory effects was used. RESULT(S): Six randomized and prospective trials involving 865 patients and 1156 cycles were identified. There was remarkable heterogeneity among the different studies concerning methodology, especially regarding ovarian cycle management and the timing of inseminations. Although the pregnancy rate per cycle was somewhat higher in the two-inseminations-per-cycle group (14.9% vs. 11.4%), there were no statistically significant differences (relative risk = 1.34; 95% confidence interval 0.90-1.99). CONCLUSION(S): No significant differences were observed when two inseminations per cycle were performed, compared with one insemination. There was great heterogeneity concerning ovarian management and insemination timing. This heterogeneity hampered the analysis. We detected a better pregnancy rate with two inseminations vs. one insemination when clomiphene citrate with or without gonadotropins and 5000 IU of hCG were used. More studies are necessary to ascertain whether this is true or merely an artifact from the multiple subgroups analysis.     

Superovulation with buserelin and gonadotropins dramatically improves the success rate of intrauterine insemination with husband's washed semen

The purpose of this study was to determine the effectiveness of intrauterine insemination with husband's washed semen during stimulated cycles using a combined treatment of GnRH agonist (buserelin) and gonadotropins. 47 infertile couples were studied; 25 couples were treated with buserelin and gonadotropins (study group) and 22 (control group) received clomiphene citrate alone. Indications for treatment, in both groups, were male subfertility, cervical factor or unexplained infertility. For sperm preparation, the same swim up technique in both groups was used. In the study group, 15 pregnancies were achieved (pregnancy rate: 60%) whereas only 5 pregnancies were achieved in the control group (pregnancy rate: 22.7%) (p less than 0.01). The pregnancy rate per cycle was 17.6 and 4.8 respectively (p less than 0.01). The mean number of follicles per cycle (+/- SEM) was 3.6 +/- 0.2 and 1.7 +/- 0.07, respectively (p less than 0.0005). Comparing successful and unsuccessful cycles a difference was observed only among the levels of 17 beta E2, both per cycle and per follicle/cycle (1075 +/- 165.4 vs 721 +/- 57.6 and 319.8 +/- 42.6 vs 219.9 +/- 17.8; p less than 0.01 and p less than 0.0005 respectively). The authors conclude that intrauterine insemination with washed sperm during stimulated superovulatory cycles is a successful mode of therapy in all couples with infertility not associated with anatomic damage of the adnexa or with chronic anovulation.     

Intrauterine insemination as treatment for antisperm antibodies in the female

Ninety-one women with long-standing infertility in the presence of humoral antisperm antibodies (ASA) underwent 473 cycles of intrauterine insemination of washed sperm (IUI), resulting in 26 pregnancies. Nine pregnancies were achieved in 67 women who underwent 285 IUI during unstimulated cycles (13% pregnancy rate; 3% pregnancy/cycles of treatment). Twenty women underwent 86 IUI after clomiphene citrate (CC) stimulation, resulting in 6 pregnancies (30%; 7% per cycle), while 28 underwent 102 cycles of IUI after human menopausal gonadotropins (hMG) stimulation, resulting in 11 pregnancies (39%; 11% per cycle). Twenty-one of the 26 pregnancies (81%) were achieved in the first 2 IUI cycles. During unstimulated and CC IUI cycles, all pregnancies occurred in the first two cycles of treatment, while with hMG stimulation pregnancies also occurred in the third, fourth, and fifth IUI cycles. Nine of these 91 women subsequently conceived spontaneously, and three others conceived through in vitro fertilization. Only 6 of the 38 pregnancies resulted in spontaneous abortion (16%). Thus, pregnancies achieved in women with ASA have no increased risk of abortion.     

Fallopian tube sperm perfusion: the impact of sperm count and morphology on pregnancy rates

BACKGROUND AND OBJECTIVE: To evaluate the effect of changed criteria for sperm count and morphology when performing fallopian tube sperm perfusion (FSP) in unexplained infertility. PATIENTS AND METHODS: We report on a longitudinal study in which two periods of insemination cycles are compared. One hundred and eighty-three couples who started 361 stimulation cycles intended for FSP were included in the first period and 190 couples starting 303 cycles in the second period. The sperm requirement in the first study period was at least 7 million sperm in the prepared test sample. The FSP cycle included downregulation, controlled ovarian hyperstimulation (COH), ovulation induction and intrauterine and intrafallopian tube insemination using a sperm suspension of 3 mL volume. To avoid high-order multiple pregnancies, cycles at risk were converted to in vitro fertilization (IVF). Based on the results from the first period, sperm requirements were lowered to a sperm count of 3 million and at least 5% normal morphology according to strict criteria. RESULTS: FSP was performed in 51% and 60% of started cycles during the two periods with similar pregnancy (24% and 23%) and birth (15% and 19%) rates. Neither sperm count nor morphology above the requirements affected pregnancy rates. IVF-converted, completed cycles reached equal pregnancy (41%) and delivery (32%) rates in both periods. Multiple pregnancy rates were higher after IVF (38%) than after FSP (24%). CONCLUSION: The lowered requirements for sperm count and morphology have not impaired pregnancy results after FSP. Patients who either completed an FSP cycle or had their cycle converted to IVF were all at high risk of multiple pregnancy.