Andrology: Strategies in frozen donor semen procreation

Data were analysed from 710 couples who had been assessed todetermine the effectiveness and the drawbacks of three differentmethods of insemination using frozen donor semen. Intracervicalinsemination (ICI) was the first method used when the womenhad no tubal disorder: 255 pregnancies were achieved in a totalof 2558 cycles (10%). Intrauterine insemination (IUI) associatedwith ovarian stimulation resulted in 152 pregnancies over 966cycles (16%). In-vitro fertilization (IVF) was proposed after12 insemination failures using either of the other methods orwhen the initial gynaecological examination had revealed abnormalitiessuch as tubal occlusions; 48 pregnancies were obtained in 262cycles (18.3%). The pregnancy rate using ICI was significantlyhigher when two inseminations were performed per cycle, comparedwith one insemination per cycle (12.3 versus 7%, P < 0.001).The number of motile spermatozoa per straw was correlated withthe pregnancy rate when using ICI, rising from 9% with <4X10⁶motile spermatozoa to 13.8% with 4–8X10⁶ and 17.2% with>8X10⁶. No relationship was found between the number of motilespermatozoa and the pregnancy rate using IUI and IVF. The incidenceof primary ovulatory disorder was higher among women whose husbandswere oligozoospermic than among those whose husbands were azoospermic(19 versus 9%, P < 0.01), but ovarian stimulation improvedthe fecundity of subfertile women. The outcome of pregnancieswas also analysed for the three methods. From these data, strategicplans have been proposed to maximize the pregnancy rate forwomen undergoing therapeutic donor insemination with frozensemen.     

Intrauterine insemination: critical analysis of a therapeutic procedure.

Donor intrauterine insemination with washed spermatozoa (fresh semen) was performed in 36 women (63 cycles) whose husbands had azoospermia due to primary or secondary testicular failure. Simultaneously a control group of 76 couples (156 cycles) with proven fertility, who had recently discontinued mechanical non-hormonal contraception, were encouraged to have sexual intercourse during the fertile period. The age of the women was similar in both groups and the timing criteria were also similar. The pregnancy rate per woman was 50% in the donor insemination group and 47.4% in the control group (difference not significant). The pregnancy rate per cycle was 28.6% in the artificial insemination group and 23.1% in the control, natural insemination group (difference not significant). The number of artificial or natural insemination cycles required to achieve pregnancy was similar in the study and control groups. This study suggests that when the inseminating spermatozoa and female partner are normal, as occurs in the donor insemination group, intrauterine insemination is as efficient as natural insemination in achieving pregnancy but is not more successful.     

Fallopian tube sperm perfusion used in a donor insemination programme.

Ninety-six couples were enrolled in a programme of Fallopian tube sperm perfusion (FSP). FSP is a method combining ovarian stimulation, ovulation induction and intra-uterine insemination with a 4 ml volume of sperm suspension. Frozen/thawed donor semen was used in all cycles. A total of 196 treatment cycles were started and of these 172 were completed. Twenty cycles were cancelled because of maturation of too many follicles, a low ovarian response, or formation of ovarian cysts. Five of the women enrolled in the programme did not have any inseminations. Forty-eight pregnancies occurred (27.9% per cycle) among 45 women (49.5%). There were five spontaneous abortions and one ectopic pregnancy. Sixteen pregnancies are on-going (greater than 12 weeks) and 26 women have delivered (including two sets of triplets and one set of twins). The pregnancy rate declined from the first attempt (34.1%) to the fourth attempt (14.3%). The pregnancy rate was significantly higher in women with three to five mature follicles compared to women with two or fewer mature follicles (P less than 0.05). Cycles in which human chorionic gonadotrophin (HCG) was administered on day 11 or later had a higher pregnancy rate than cycles where HCG was administered on day 10 (P less than 0.01). There was no difference in pregnancy rates between insemination with 8-10 x 10(6) motile spermatozoa and insemination with greater than 30 x 10(6) motile spermatozoa. FSP used in a programme of artificial insemination by donor using frozen/thawed donor semen is relatively simple to perform and gives a high pregnancy rate per cycle.     

Intrauterine insemination and controlled ovarian hyperstimulation in cycles before GIFT

We have combined intrauterine insemination (IUI) and controlledovarian hyperstimulation (COH), for the treatment of infertilitydue to different aetiologies, prior to performing GUT. To date,we have treated 186 patients over a total of 489 cycles. Themean age of the patients was 34.1 ± 4 years and the meanduration of infertility was 4.8 ± 2.8 years. Folliculardevelopment was induced with human menopausal gonatrophin (HMG).Patients were monitored using serum oestradiol determinationsand ovarian ultrasound. Two intrauterine inseminations wereperformed 12 and 36 h after HCG injection. Semen samples wereprepared utilizing one of two techniques, swim-up or Percollgradient. A total of 33 pregnancies have occurred, the grosspregnancy rate being 17.7% per patient and 6.7% per cycle. Thecumulative pregnancy rate was 30%. Thirty-one pregnancies (94%)occurred within the first four cycles of treatment. During thesame period of time, the pregnancy rate per cycle in patientstreated with gamete intra-Fallopian transfer (GIFT) was 32.9%.Our data suggest that IUI combined with COH can result in pregnancyin a significant proportion of patients, but that the efficiencyper cycle of the technique is significantly lower than GIFT.     

Single versus double insemination: a retrospective audit of pregnancy rates with two treatment protocols in donor insemination

Our objective was to evaluate the effect of a change in treatment protocols, suggested following an inspection visit by the regulatory authority, from single to double inseminations during donor insemination treatment cycles. We therefore conducted a retrospective audit of pregnancy rates in the reproductive medicine clinic of a major teaching hospital. All patients were treated for male factor infertility by donor insemination, without ovulation induction with gonadotrophins between October 1992 and December 1995. The main outcome measures were cumulative conception and live birth rates. During the study period 250 patients underwent treatment and 650 single insemination and 277 double insemination treatment cycles were undertaken. The pregnancy rate per cycle was 0.054 and 0.119 for single and double insemination respectively. After six cycles the cumulative pregnancy rates were 0.28 and 0.47 and the take-home baby rates were 0.25 and 0.37 for single and double inseminations respectively. The change in practice from single to double insemination resulted in a doubling of the pregnancy rate per treatment cycle. Cumulative pregnancy rates after two treatment cycles of double insemination were comparable with those achieved after six cycles of single insemination. These results have significant implications for both patients and purchasers.      

The use of human follicular fluid in gamete intra-fallopian transfer

We undertook a prospective study to compare our gamete intra-Fallopian transfer (GIFT) procedure with or without the use of human follicular fluid (FF) as a constituent for the final spermatozoal suspension and as the tubal transfer medium for both eggs and spermatozoa. We routinely perform an intrauterine and intracervical insemination (IUI and ICI) following GIFT, and FF or culture medium was used accordingly as a constituent in this spermatozoal suspension also. When FF was used (26 cycles), clear FF taken from the first egg-bearing follicle was sterilized by micropore filtration, gassed with 5% CO2 in air and warmed to 37 degrees C. This FF was then used to dilute the spermatozoal suspension (50:50, v/v) for both tubal, uterine and cervical inseminations at least 30 min before transfer, and all transferable eggs were placed into this FF before transfer. Alternatively (30 control cycles), eggs and spermatozoa were prepared and transferred in Earle's medium supplemented with 10% pooled fetal cord serum. The FF and control patient groups were relatively homogeneous, with no statistically significant differences in ovarian response, oocyte retrieval or transfer or seminal profiles. The outcome of the GIFT procedures using FF or culture medium showed no significant advantage of the use of FF. The clinical pregnancy rate was similar in both groups: 50% (15/30) control; 46.2% (12/26) FF.     

A prospective, randomized, cross-over comparison of two methods of artificial insemination by donor on the incidence of conception: intracervical insemination by straw versus cervical cap

In a prospective, randomized study of insemination with donor semen, intracervical insemination by straw was compared with insemination using a cervical cap with an intracervical reservoir. A total of 91 patients completed 486 treatment cycles. There were no significant differences in age, parity, indication for insemination by donor, or method of cycle monitoring between women who became pregnant and those who did not conceive with either insemination method. In 236 standard intracervical insemination cycles, 14 patients became pregnant (5.9% per cycle), whereas 38 patients conceived in 250 cervical cap cycles (15.2% per cycle). Both the crude pregnancy rates and the cumulative pregnancy rates calculated by the Kaplan-Meier life-table method were significantly different (chi(2)-test, P < 0.001, and log-rank test, P < 0.005 respectively). Pregnancy rates in artificial insemination with cryopreserved donor semen may be improved by the use of a cervical cap when compared to cervical insemination by straw. The use of the cervical cap may prolong the exposure of the spermatozoa to the cervical mucus and prevent the backflow of semen into the vagina.      

Prospective randomized comparison of intrauterine and intracervical insemination with donor spermatozoa

From March 1990 to September 1993, 20 women underwent a totalof 89 cycles of intracervical inseminations with donor semen(ICI) and 23 women underwent 67 cycles of intrauterine inseminationswith donor semen (IUI). The women were assigned to the two groupsrandomly, but ensuring that the ages of the women and pathologiesof the male partner (azoospermia or severe oligozoospermia)were similar in the two groups. There was no significant differencebetween the characteristics of the two groups and the methodused to induce ovulation (HMG/HCG) was identical. Two semenstraws were used for each insemination cycle. Semen was preparedfor IUI on a Percoll gradient. Thirteen clinical pregnancieswere obtained in the IUI group (19.4% of the attempts) and sixin the ICI group (6.75%). After six cycles of insemination,75.4% of the women of the IUI group obtained a pregnancy, ascompared to 35% in the ICI group. These good results may bedue to the method of induction of ovulation, but also to thetechnique itself, increasing the number of motile spermatozoaat the site of fertilization. The time taken to obtain a pregnancyis thus shorter with IUI than with ICI, and the number of semenstraws required is smaller. In-vitro fertilization (IVF) shouldbe proposed after six failures by IUI.     

Intrauterine insemination with frozen donor sperm. Pregnancy outcome in relation to age and ovarian stimulation regime

BACKGROUND: The success of intrauterine insemination with donor semen (IUI-DI) is likely to be influenced by a number of variables, including age and ovarian stimulation (OS) regime. METHODS AND RESULTS: A retrospective analysis of 1056 treatment cycles in 261 women (212 single heterosexuals and 49 lesbians) was conducted to assess the influence of these two variables on pregnancy outcome during IUI-DI. The overall pregnancy rate was 10.6%, being 18.5% for women <35 years, 11.9% in women 35-40 years and 5.4% in women >40 years (P < 0.05). The cumulative pregnancy rate (CPR) after eight cycles was 0.86, 0.51 and 0.32 respectively (P < 0.05). A total of 445 inseminations were performed following spontaneous ovulation, 360 following OS with clomiphene citrate (CC) and 251 with hMG, the pregnancy rate per cycle being 13, 7.2 and 11.2% respectively. There was no statistically significant difference in the pregnancy rate per cycle, CPR or multiple pregnancy rate in the three treatment groups. CONCLUSIONS: These results indicate that the use of OS with either CC or hMG in women without ovulatory dysfunction does not improve the pregnancy rate during IUI-DI. The only factor associated with reduced effectiveness of fertility treatment was age, confirming that IUI is a poor treatment option for women >40 years of age.     

Infertility: Spontaneous ovulatory cycle donor insemination programme: prognostic indicators of a successful pregnancy

The effects of female and male infertility factors as well asthe insemination regime on the outcome of donor insemination(DI) during 1001 spontaneous ovulatory cycles were assessed.Overall, the average monthly fecundability was 4.4% and thecumulative conception rate after nine cycles was 45%. FemaleDI recipients’ age, nulligravidity or the presence ofother infertility factors were associated with a significantlylower pregnancy rate. DI recipients of azoospermic partnershad a significantly higher pregnancy rate. The likelihood ofa successful pregnancy was higher when more frequent (1) inseminationswere used or in association with higher cervical score and largerfollicle diameter at the time of insemination. We suggest thatfemale recipients of DI should be fully investigated beforecommencing DI treatment. Early resort to other methods of assistedreproduction should be considered in DI recipients aged 35 years,or in younger women if they fail to conceive after nine cyclesof DI. More frequent and better timing of inseminations is expectedto improve the fecundability rate during spontaneous ovulatoryDI cycles.     

The use of gamete intra-Fallopian transfer with donor spennatozoa after failed donor insemination

The objective of this study was to assess the efficacy of gameteintra-Fallopian transfer (GIFT) in couples who had failed toconceive by donor insemination. The study was designed as aretrospective analysis of couples who entered the GIFT programmeafter 12 failed cycles of donor insemination. It took placein a comprehensive reproductive clinic with large donor inseminationand in-vitro fertilization/GIFT programmes. A total of 197 patientsreceived a total of 350 treatments from 1985 until 1992. Couplesentered the GIFT programme with the routine stimulation andmonitoring. The only difference was that frozen spermatozoawere used for the insemination. The main outcome measure waspregnancy, defined as a positive -human chorlonic gonadotrophin(>30 IU/1) at 16 days after replacement of gametes. The overallpregnancy rate achieved was 31% per cyde. Life table analysisshowed a cumulative pregnancy rate of 75.4 ± 5.7% afterfour cycles and 96.0 ± 2.7% after eight cycles. It wasconcluded that the use of GIFT with donor spermatozoa is a highlyeffective treatment and should be offered to all couples whofail to conceive with donor insemination.     

A new rapid and effective method for treatment of unexplained infertility

BACKGROUND: Artificial insemination (intrauterine insemination by husbandor artificial insemination by husband) is often tried as firsttreatment for couples with unexplained infertility. Pertubationhas previously proved to increase the chance of achieving pregnancyfor these couples. The effect of pertubation on fertility canbe mechanical as well as anti-inflammatory by using a substancethat inhibits phagocytosis of the spermatozoa. The objectiveof the study was to investigate the effect on pregnancy rateof pre-ovulatory pertubation with low-dose lignocaine duringclomiphene citrate and insemination cycles for couples withunexplained infertility. METHODS: In a prospective, open study, the patients were randomized,the day before ovulation, during a clomiphene citrate stimulatedcycle to either pertubation with low-dose local anaestheticor no pertubation before insemination. RESULTS: A total of 130 cycles were studied, 67 of which were randomizedto pre-ovulatory pertubation and 63 to no pertubation treatment.There were 14.9% (n = 10) clinical pregnancies in the pertubatedgroup compared with 3.2% (n = 2) in the group without pre-ovulatorypertubation (P < 0.05). CONCLUSIONS: The pertubation treatment significantly enhanced the clinicalpregnancy rate and was well tolerated. No complications werenoted. The combined treatment of clomiphene citrate, pertubationand insemination can be used as a cost-effective, first-linetreatment for couples with unexplained infertility.     

The outcome of intracytoplasmic sperm injection in patients with retrograde ejaculation.

The objective of this retrospective clinical study was to assess the benefit of assisted fertilization in cases of anejaculatory infertility due to retrograde ejaculation. We report the outcome of intracytoplasmic sperm injection (ICSI) treatment. In 16 couples in which the men suffered from retrograde ejaculation. We performed 35 cycles of ICSI with spermatozoa retrieved from post-ejaculatory urine. The patients had been instructed to alkalinize the urine by ingesting sodium bicarbonate before the procedure. The fertilization rate averaged 51.2%. Seven clinical pregnancies were achieved. Three spontaneous first trimester abortions occurred, but three live offspring were delivered and one pregnancy is ongoing. In conclusion, the use of ICSI may be feasible for patients with retrograde ejaculation who are resistant to medical treatment and whose sperm quality is so low or unpredictable that intrauterine insemination or conventional methods of in-vitro fertilization are not possible.     

The use of urine LH detection kits to time intrauterine insemination with donor sperm

BACKGROUND: The study was carried out to determine the most likely time of day for the onset of the LH surge as detected using urine LH dipsticks, and to calculate the optimum time interval from the onset of the LH surge to intrauterine insemination (IUI). METHODS: A prospective study of 1540 cycles of IUI with donor sperm at Cleveland Fertility Centre, Middlesbrough, between June 1990 and February 2004. Only 951 cycles (where a positive urine LH dipstick result was immediately preceded by a negative result) were included in our study. To determine the best time interval between the onset of the LH surge and IUI, women were divided into five subgroups according to the positive urine test-IUI time interval and the pregnancy rate and live birth rate per cycle were calculated for each group. RESULTS: The first positive test was most frequently (44.5%) found at lunch-time (11:00-15:00). The live birth per cycle achieved was 5.6% when the insemination was performed 18-23 h from the first detection of the LH surge, and 11.7% when it was performed between 24 and 42 h. The live birth rate declined to 6.5% when IUI was performed later than that. Overall, no significant differences were discovered in live birth or pregnancy rate when insemination was performed at any of the time points between 18 and 53 h. CONCLUSION: Our study suggested that lunch-time is the best time to check for the LH surge using urine dipsticks and insemination at any time between 18 and 53 h after the onset of the surge will produce optimal results.     

Slow release intrauterine insemination versus the bolus technique in the treatment of women with cervical mucus hostility.

Thirty-eight infertile women with cervical mucus hostility were divided at random into two groups for intrauterine insemination with prepared husband's semen. Eighteen women started with slow release (treatment A) and 20 with bolus (treatment B) intrauterine insemination in a cross-over study for four alternating cycles. Insemination was timed 30-36 h after a positive luteinizing hormone (LH) surge or injection of 5000 IU of human chorionic gonadotrophin, given at a follicular diameter of 18 mm during ultrasonically monitored, unstimulated cycles. A Grasby auto-syringe driver (type MS16) was used for the slow release intrauterine insemination to deliver 50 x 10(3) motile spermatozoa every minute for 3 h. Bolus intrauterine insemination was performed by deposition of 0.6 ml of prepared semen without changing the count from the swim-up portion of the washed spermatozoa. A total of 13 patients conceived, nine from 60 cycles of treatment A and four from 66 cycles of treatment B (chi-squared = 2.7143, P less than 0.05 using one-tailed statistics).     

Intrauterine insemination: evaluation of the results according to the woman's age, sperm quality, total sperm count per insemination and life table analysis

We report on 332 infertile couples who underwent 1115 cyclesof intrauterine insemination (IUI) with washed husband's semen.The indication for IUI was an abnormal post-coital test dueto either a male or cervical infertility factor. The mean numberof IUI cycles per patient was 3.4, the overall pregnancy rate18, 7%, and the pregnancy rate per cycle 5.6%. The cumulativepregnancy rate calculated by life table analysis showed that16.0% of pregnancies occurred in the first three treatment cycles,while the cumulative pregnancy rate was 26.9% by the sixth cycle.The outcome of the therapy was adversely affected if the woman'sage was >39 years and/or total motile sperm count per inseminationwas <1X106. No pregnancy occurred in women older than 44years or in cases with a total motile sperm count before semenpreparation of <1X106.     

Intrauterine donor insemination in single women and lesbian couples: a comparative study of pregnancy rates

The outcome of intrauterine donor insemination (IUI-DI) with frozen spermatozoa was analysed retrospectively in 675 cycles in single women (n = 122; 536 cycles) and lesbian (n = 35; 139 cycles) couples. The lesbian patients were younger at the initiation of treatment (mean 34.5 years; range 26-44) than the single women (mean 38.5; range 29-47) (P = 0.005). Clinical pregnancy rate was 36% in single women and 57% in lesbians (P < 0.05), the cumulative pregnancy rate after six cycles being 47% and 70% respectively, although the outcome was similar when related to age. The miscarriage rate was higher (35%) in single women than in lesbians (15%; P < 0.05), the rate being independent of maternal age. There were no apparent differences seen between the two groups with respect to the possible effect of parity, duration of infertility, causes of infertility and type of treatment at initiation of treatment; the sole exception was that the age of lesbian women was statistically significantly younger than that of single women (P < 0.005). When corrected for age, the pregnancy rates and complications were lower and higher respectively in single women but these differences did not reach statistical significance. However, the disparity between the treatment outcomes of single women and lesbian patients of similar ages may also reflect the fact that single women are likely to have failed to conceive for a period of time prior to referral to a specialist centre for treatment.     

不同病因不孕症宫腔内人工授精1640周期疗效分析

目的分析不同病因不孕症行夫精宫腔内人工授精(AIH/IUI)的疗效。方法对2007年1月-2007年12月在浙江省妇保院生殖中心门诊1244对不孕症实施治疗1640周期,根据不同的病因分析比较统计临床妊娠率。结果每周期的临床妊娠率为11.10%,每例临床妊娠率为14.63%。原发不孕组妊娠率高于继发不孕妊娠率(18.4%对9.7%),管性因素不孕组临床妊娠率(4.4%)显著低于不明原因(25.08%)、排卵障碍(18.48%)、男性因素(12.59%)和子宫内膜异位症组(12.62%)(P0.01),后四组妊娠率差异无显著性但以不明原因组最高。女方年龄影响妊娠率。结论夫精宫腔内人工授精(AIH/IUI)治疗非输卵管因素引起不孕疗效甚佳。     

不同促排卵方案联合宫腔内人工授精疗效分析

目的比较不同促排卵方案联合宫腔内人工授精（intrauterine insemination,IUI）治疗不孕症的疗效。方法对204例不孕症患者371个周期行IUI治疗,随机分为4组：自然周期（natural cycle,NC）组共102个周期,克罗米酚（Clomiphene,CC）组98个周期,人绝经期促性腺激素（human menopausal gonadotropin,HMG）/人绒毛膜促性腺激素（human chorionic gonadotropin,HCG）（HMG/HCG）组120个周期,CC/HMG/HCG组51个周期,比较不同促排卵方案的治疗效果。结果CC/HMG/HCG组（19.6%）与HMG/HCG组（20.0%）的周期妊娠率显著高于NC组（6.9%）及CC组（8.2%）（P〈0.01）。CC/HIMG/HCG组的HMG用药量和用药天数显著小于HMG/HCG组（P〈0.05）。结论CC/HMG/HCG和HMG/HCG促排卵联合IUI均能提高IUI治疗不孕症的妊娠率,CC/HMG/HCG促排卵药费支出少,更具有优势。     

Is waiting for an endogenous luteinizing hormone surge and/or administration of human chorionic gonadotrophin of benefit in intrauterine insemination?

This retrospective study was undertaken to investigate the observation that the probability of pregnancy was higher with intrauterine insemination (IUI) when human chorionic gonadotrophin (HCG) was administered after the onset of the luteinizing hormone (LH) surge. A total of 219 patients who had 524 IUI cycles was included in this study. IUI cycles were divided into three groups: group 1, patients who had an endogenous LH surge but no HCG; group 2, patients given HCG after an endogenous LH surge was observed; and group 3, patients given HCG before an endogenous LH surge could be demonstrated. The overall clinical pregnancy rate was 16%. Forty-two (19.2%) patients had 91 cycles with their partner's semen, while 177 (80.8%) used donor semen in 433 cycles; clinical pregnancy rates were 12.1% and 16.9% respectively. There was no significant difference in pregnancy rate per cycle between patients in group 1 (12.7%) compared with those in groups 2 (15.6%) or 3 (20.5%). We could not establish any benefit in waiting for a spontaneous LH surge before administering HCG in the presence of a mature follicle(s) in this study. This strategy avoids further monitoring to detect the LH surge, allowing treatment to be planned for a time convenient to the patient.