Is controlled ovarian stimulation in intrauterine insemination an acceptable therapy in couples with unexplained non-conception in the perspective of multiple pregnancies?

BACKGROUND: Controlled ovarian stimulation (COS) with intrauterine insemination (IUI) is a common treatment in couples with unexplained non-conception. Induction of multifollicular growth is considered to improve pregnancy outcome, but it contains an increased risk of multiple pregnancies and ovarian hyperstimulation syndrome. In this study the impact of the number of follicles (>14 mm) on the ongoing pregnancy rate (PR) and multiple PR was evaluated in the first four treatment cycles. METHODS: A retrospective cohort study was performed in all couples with unexplained non-conception undergoing COS-IUI in the Academic Hospital of Maastricht. The main outcome measure was ongoing PR. Secondary outcomes were ongoing multiple PR, number of follicles of >or=14 mm, and order of treatment cycle. RESULTS: Three hundred couples were included. No significant difference was found in ongoing PR between women with one, two, three or four follicles respectively (P=0.54), but in women with two or more follicles 12/73 pregnancies were multiples. Ongoing PR was highest in the first treatment cycle and declined significantly with increasing cycle order (P=0.006), while multiple PR did not change. CONCLUSIONS: In COS-IUI for unexplained non-conception, induction of more than one follicle did not improve the ongoing PR, but increased the risk of multiple pregnancies. Multiple PR remained high in the first four cycles with multifollicular stimulation. Therefore, in order to reduce the number of multiple pregnancies, in all IUI cycles for unexplained non-conception monofollicular growth should be aimed at.     

Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation

BACKGROUND: To compare the clinical results and the cost-effectiveness of using the aromatase inhibitor, letrozole, in conjunction with FSH and FSH alone for controlled ovarian stimulation (COS) in patients undergoing intrauterine insemination (IUI) for a variety of indications. METHODS: Four hundred and thirty-two consecutive patients who underwent 872 IUI cycles were included. The study population was composed of two groups. Group I included 308 patients who underwent 589 IUI cycles with letrozole and FSH for the following indications: anovulation (143 cycles), male factor infertility (147 cycles), unexplained infertility (250 cycles), endometriosis (18 cycles) and combined indications (31 cycles). Group II included 124 patients who underwent 283 IUI cycles who received FSH only for the following indications: ovarian factor infertility (82 cycles), male factor infertility (66 cycles), unexplained infertility (114 cycles), endometriosis (13 cycles) and other indications (8 cycles). Main outcome measures included number of mature follicles >16 mm in diameter, dose of FSH used per cycle, clinical pregnancy rate and cost-effectiveness ratio per pregnancy. RESULTS: FSH dose required for ovarian stimulation was significantly lower when letrozole was used (P < 0.0001). Although a significantly higher number of follicles >16 mm and endometrial thickness at the day of hCG administration (P < 0.0001) were observed in Group II, pregnancy rate per started (14.4 versus 15.9%) and per completed cycles (15.77 versus 18.07%) was the same in Group I and Group II, respectively. IUI cancellation rate was significantly lower with letrozole treatment (P = 0.05%). The cost per cycle was significantly lower in Group I versus Group II (468.93 Can dollars +/- 418.18 versus 1067.28 +/- 921.43; P < 0.0001). The cost-effectiveness ratio was 3249.42 dollars in the letrozole group and 6712.00 dollars in the FSH-only group. CONCLUSION: A letrozole-FSH combination could be an effective ovarian stimulation protocol in IUI cycles. Such a protocol may be more cost-effective than FSH alone because of the difference of FSH dose and cost. A randomized controlled trial is needed to further substantiate this finding.     

Infertility: Intra-uterine insemination or timed intercourse after ovarian stimulation for male subfertility? A controlled study

In this randomized trial we investigated whether intra-uterineinsemination (IUI) in couples with male subfertility leads toa higher probability of conception than timed intercourse afterovarian stimulation with human menopausal gonadotrophin (HMG)and human chorionic gonadotrophin (HCG). A total of 76 couplesstarted 249 cycles, of which 47 were cancelled to prevent multiplepregnancies or hyperstimulation. After 202 completed treatmentcycles, 15 pregnancies occurred, 11 after IUI and four aftertimed intercourse. The pregnancy rate per completed cycle withIUI was 10.3% (95% confidence interval: 5.5–17.5%) and4.2% (1.2–10.1%) with timed intercourse. Compared withthe estimated spontaneous chance to conceive, IUI after ovarianstimulation appeared to be more effective in the first threecycles. We conclude that in subfertile couples with a male factor,IUI tends to improve the probability of conception as comparedto timed intercourse when ovarian stimulation is applied, andwe advise such treatment for three cycles.     

Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. 'Effective treatment' or 'not a natural choice'?

Helping couples to choose appropriate therapy for their unexplained subfertility demands a review of evidence for treatment benefit and harm, in the context of both patients' and clinicians' experience and perspective. Ovulation induction (OI) with clomiphene (CC) or gonadotrophin (FSH) and intrauterine insemination (IUI) are often chosen before resorting to IVF. The appropriateness of starting with these low and intermediate intensity treatments is supported by evidence that CC/IUI increases cycle fecundity two- to three-fold, and FSH/IUI, three- to five-fold over the baseline chance of pregnancy in this patient group. While both OI/IUI and IVF have adverse effects which deserve vigorous attention, particularly multiple pregnancy and ovarian hyperstimulation syndrome (OHSS), the balance between benefits and costs often favours OI/IUI. The cost per live birth and potential for OHSS appears lower with OI/IUI, and the proportion of multiple pregnancies similar to that seen with IVF. For these as well as physical and spiritual reasons, OI/IUI is often a natural starting point for couples, especially when female age and duration of subfertility are favourable.     

A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility

BACKGROUND: Controlled ovarian hyperstimulation with intrauterine insemination (IUI) is a widely accepted treatment for unexplained and male subfertility. No consensus exists about the drug of first choice to be used as hyperstimulation. This randomized multicentre trial using a parallel design compares the efficacy of clomiphene citrate (CC) with that of recombinant FSH (rFSH). METHODS: Couples with primary unexplained or male subfertility were randomized to receive CC or rFSH for ovarian hyperstimulation. The treatment was continued for up to four cycles unless pregnancy occurred. Cycles with more than three follicles were cancelled. Cumulative pregnancy rates and live birth rates were primary outcomes. Cancellation during treatment and multiple birth rates are secondary outcomes. Results were analysed following the intention-to-treat principle. RESULTS: Seventy couples with male subfertility and 68 couples with unexplained subfertility were included. Seventy-one women received CC, and 67 received rFSH. Twenty-seven pregnancies were observed in the CC group (38%) and 23 in the rFSH group (34.3%) relative risk (RR) 1.11 [95% confidence interval (95% CI) 0.71-1.73]. The live birth rate was 28.2% (20/71) and 26.9% (18/67) for CC and rFSH, respectively, RR 1.05 (95% CI 0.61-1.80). Overall, the live birth rates per cycle were 10% for CC-stimulated and 8.7% for rFSH stimulated cycles. The total multiple pregnancy rate was 6.0%. Thirty-five cycles (8.6%) were cancelled because of four or more follicles (CC, n = 17; rFSH, n = 18). CONCLUSIONS: In couples with primary unexplained or male subfertility participating in an IUI program, ovarian hyperstimulation can be achieved by CC or rFSH. No significant difference in live birth rates between CC and rFSH was observed. Being less expensive, CC seems the more cost-effective drug and therefore, can be offered as drug of first choice.     

Infertility: Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles

At present, there is general agreement that ovarian stimulationimproves pregnancy rates after intra-uterine insemination (IUI).Also, ovulation induction with gonadotrophins is associatedwith higher success rates than clomiphene citrate in IUI cycles.However, the drawbacks to the use of gonadotrophin stimulationbefore IUI include the risks of ovarian hyperstimulation andmultiple gestation, and the relative cost of a treatment cyclein view of the medication costs and the need for increased monitoringby hormone assays and ultrasonographic measurements. In thepresent prospective randomized trial, the efficacy and safetyof ovarian stimulation with clomiphene citrate (50 mg/day for5 days) and IUI (clomiphene/IUI group) were compared with thoseof late low-dose pure follicle stimulating hormone (FSH, 75IU/day from day cycle 7 until the leading follicle reached >17mm in diameter) and IUI (FSH/IUI group) in ovulatory women whowere infertile because of unexplained infertility (n=40)or malesubfertility (n =60). The mean length of treatment in the FSHgroup was 6.4±2.5 days. Multiple follicular developmentwas seen in 25% of clomiphene-stimulated cycles but only in8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUIand FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively(P=0.02). All pregnancies obtained were singleton. There weretwo and one clinical abortions in the clomiphene/IUI (50%) andFSH/IUI (8%) groups respectively. No patient developed ovarianhyperstimulation syndrome. Use of our therapeutic scheme, whichproved to be efficacious, safe and economic for ovarian stimulationin IUI cycles, is advocated before the institution of in-vitrofertilization (IVF) or gamete intra-Fallopian transfer (GIFT)therapy in infertile patients with patent Fallopian tubes. Thislate low-dose technique of administering pure FSH is suitablefor use in offices without immediate access to oestradiol results.     

Vaginal misoprostol enhances intrauterine insemination

This study examined whether the prostaglandin E(1) analogue misoprostol (400 microgram), when placed vaginally at the time of intrauterine insemination (IUI) improves pregnancy rates. A prospective, placebo-controlled, randomized and double-blind study involving 274 women in 494 IUI cycles resulted in a total of 64 pregnancies (13% per cycle). Misoprostol cycles totalled 253, with 43 pregnancies (17% per cycle), whereas placebo cycles totalled 241, with 21 pregnancies (9% per cycle). The cumulative pregnancy rate with misoprostol treatment was significantly greater than with placebo (P = 0.004, Cox proportional hazards regression). The benefit of misoprostol was seen in clomiphene cycles (14 versus 4%, P = 0.006), and was indicated in FSH cycles (33 versus 15%, borderline significance) and natural cycles (15.6 versus 7.7%, not significant), but was not seen in clomiphene/FSH cycles (18.2 versus 23.5%, not significant). Misoprostol treatment did not increase pain score on the day of IUI (1.1 versus 1.4) and at 1 day post IUI (0.6 versus 0.8). Complications were rare in both groups [six (2%) subject cycles in the misoprostol cycles compared with two (1%) in the placebo group]. It is concluded that the use of vaginal misoprostol may improve the chance for pregnancy in women having IUI in a wide variety of cycle types.     

Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa

A randomized trial was carried out comparing recombinant FSH (rFSH) and highly purified urinary FSH (uFSH) in intrauterine insemination (IUI) with husbands' spermatozoa. A total of 45 women received rFSH (139 cycles), while 46 women received uFSH (155 cycles). The starting dose was 150 IU/day s.c., beginning on the second day, and on days 6-7 the dose was adjusted according to ovarian response, assessed by vaginal ultrasound and plasma oestradiol concentration. The pregnancy rate according to the intention to treat was 57.8% in rFSH versus 52.2% in uFSH, the corrected pregnancy rates 56.8% and 52.2%, and the cumulative pregnancy rates 69.6% and 61.0%, but the differences were not statistically significant. The per cycle pregnancy rate was 18.12% in rFSH and 15.48% in u-FSH, also not statistically significant. In the rFSH group, the consumption of FSH ampoules per cycle was significantly lower (19.20 +/- 7.02 versus 23. 80 +/- 10.78; P < 0.0001). The ratio of oestradiol/FSH ampoules was significantly higher in rFSH (56.45 +/- 31.26 versus 46.41 +/- 29. 25; P < 0.001). These data indicate that, in IUI cycles, rFSH has a higher potency than uFSH.     

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.     

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。     

A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination

BACKGROUND: There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation (COS) followed by timed intercourse (TI) or intrauterine insemination (IUI). METHODS: Seventy insulin-resistant primary infertile women with PCOS were randomized to receive metformin cloridrate (850 mg twice daily; group A) or placebo tablets (two tablets daily; group B) for 3 months. Three trials of COS using highly purified urinary FSH (hpFSH) plus TI/IUI were performed. Number of ampoules of gonadotrophin used, duration of the ovarian stimulation, cycle cancellation, ovulation, pregnancy, abortion, live birth, mono-ovulatory cycles, multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) rates were assessed. RESULTS: No difference between groups was detected in ovulation, cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies and OHSS rates. The mono-ovulatory cycle rates were significantly (P = 0.002) more frequent in group A than in group B, whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly (P < 0.001) higher in group A than in group B. CONCLUSION: In insulin-resistant women with PCOS, metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles.     

Comparison of different gonadotrophin preparations in intrauterine insemination cycles for the treatment of unexplained infertility: a prospective, randomized study

BACKGROUND: A comparison of the effectiveness of different gonadotrophin preparations in intrauterine insemination (IUI) cycles for patients with unexplained infertility was performed. METHODS: Two hundred and forty-one patients were prospectively randomized using computer-generated random numbers into three groups: 81 in the Follitropin alpha (Group I), 80 in the urinary FSH (uFSH) (Group II) and 80 in the hMG (Group III). The primary outcome was clinical pregnancy rate with duration of stimulation, total gonadotrophin dose, number of dominant follicles, clinical pregnancy rate, multiple pregnancy, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate being secondary outcomes. RESULTS: Clinical pregnancy rate was significantly higher in the rFSH group (25.9% in Follitropin alpha, 13.8% in uFSH and 12.5% in HMG groups; P = 0.04). There was no significant difference in terms of duration of stimulation, but mean FSH dose consumed per cycle was significantly lower in the recombinant FSH (rFSH) group compared with others (825 IU in Follitropin alpha, 1107 IU in uFSH and 1197 IU in HMG groups; P = 0.001). The number of follicles > or =16 mm diameter was significantly higher in the rFSH group compared with the uFSH and HMG groups (2.6 in Follitropin alpha, 1.3 in uFSH and 1.4 in HMG groups; P = 0.001). CONCLUSION: rFSH may result in a better outcome in IUI cycles for unexplained infertility.     

宫腔内人工授精97个周期临床分析

目的 选择84对患者97个周期的宫腔内人工授精(IUI)进行临床疗效分析。方法 按自然周期、克罗米芬(CC) 补佳乐 HCG、克罗米芬(CC) HMG HCG分为三组进行围排卵期IUI技术比较。结果 84对患者进行97含属期IUI，自然周期11个，有1例妊娠，妊娠率0．09％；克罗米芬(CC) 补佳乐 HCG组57个周期，有8例妊娠，妊娠率14．04％：克罗米芬(CC) HMG HCG组29个周期，有6例妊娠，妊娠率20．69％。结论 使用促排卵药物，尤其克罗米芬(CC) HMG HCG组，诱发排卵数目多，子宫内膜厚。妊娠率高。     

The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility

The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.3%) and seven of 48 (14.6%) respectively]. A significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) was observed in the low-dose group (8.3% versus 27.1%, P < 0.05). The incidence of moderate OHSS requiring hospitalization was reduced significantly in the low-dose group (low-dose 0% versus conventional 16.7%, P < 0.01). However, the low-dose protocol did not completely prevent multiple pregnancies. Our results suggest that the low-dose step-up FSH treatment appeared to be useful for the treatment of unexplained infertility because of the high pregnancy rates and the significant decrease in the incidence of OHSS.     

Comparison of luteal phase profile in gonadotrophin stimulated cycles with or without a gonadotrophin-releasing hormone antagonist.

BACKGROUND: The aim of our study was to explore luteal phase hormone profiles in gonadotrophin-stimulated cycles with or without gonadotrophin-releasing hormone (GnRH) antagonist therapy during intrauterine insemination (IUI). Forty-one infertile couples were recruited in this randomized clinical study. METHODS: The 19 patients included in group A were treated for 21 cycles with recombinant FSH 150 IU/day starting from day 3 of the cycle and with the GnRH antagonist cetrorelix at the dose of 0.25 mg/day starting from the day in which a follicle with a mean diameter of > or =14 mm was seen at ultrasound scan. Cetrorelix was administered until human chorionic gonadotrophin (HCG) administration. The 22 patients included in group B were administered recombinant FSH alone at the same dosage for 27 cycles. RESULTS: The two treatment groups showed a similar increase in progesterone concentration during the luteal phase. In the mid-luteal phase (day 6 after HCG), oestradiol concentrations in group B were significantly higher compared with group A (P < 0.05) but the oestradiol:progesterone ratio was similar in the two groups. Serum LH was completely suppressed during the follicular phase only in group A, concomitantly with GnRH antagonist administration. A total of six pregnancies, all ongoing, were achieved (14.3% per patient and 12.2% per cycle), equally distributed in group A and in group B. CONCLUSION: GnRH antagonists can be safely administered in gonadotrophin-stimulated IUI cycles without luteal phase supplementation because no deleterious effects of GnRH antagonist administration were noted on luteal progesterone concentration or on the duration of the luteal phase.     

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.     

Treatment of the male with follicle-stimulating hormone in intrauterine insemination with husband's spermatozoa: a randomized study

We have examined the potential of follicle-stimulating hormone (FSH) therapy for the male to improve pregnancy rates in intrauterine insemination (IUI) with husband's spermatozoa. A prospective randomized trial was performed in 148 couples undergoing IUI because of male subfertility. In the treatment group, 150 IU FSH were administered to the husbands, either i.m. or s.c., three times a week, starting 3 months before the beginning of IUI cycles and maintained until the fifth IUI cycle. In the control group no treatment was given. FSH therapy did not change semen parameters. The pregnancy rate per cycle was 13.47% in the FSH group versus 10.07% in the non-FSH group; the pregnancy rate per woman was 44.38% in the FSH group versus 37.18% in the non-FSH group. Although the pregnancy rate increase was > 30% per cycle and > 20% per woman, statistical significance was not achieved. The cumulative pregnancy rate was 59.20% in the FSH group versus 42.91% in the non-FSH group. The pregnancy rate outside the IUI cycle was 14.70% (10/68) in the FSH group versus 2.5% (2/80) in the non-FSH group, the difference being statistically significant. In conclusion, a non-significant trend towards higher pregnancy rates in IUI was observed in the FSH group.      

Intrauterine insemination: effect of the temporal relationship between the luteinizing hormone surge, human chorionic gonadotrophin administration and insemination on pregnancy rates

The optimal time period for intrauterine insemination (IUI) in relation to either luteinizing hormone (LH) surge or human chorionic gonadotrophin (HCG) administration leading to the best pregnancy rates has not been determined. In this study, 856 consecutive human menopausal gonadotrophin (HMG)-stimulated and 49 natural unstimulated IUI cycles carried out at a reproductive medicine unit affiliated with a tertiary centre were analysed in a retrospective fashion. There were three scenarios in the temporal relationship of the LH surge, HCG administration and artificial insemination. These were (group A) subjects who had an endogenous LH surge but were not given HCG; (group B) subjects who were given HCG after an observed LH surge, and (group C) subjects who were given HCG before the LH surge. The overall pregnancy rate (PR) was 16% per cycle. The PR was 9% in group A, 20% in group B and 14% in group C. The PR in group B was significantly better than group C (P = 0.04). In group B, the longer the time interval between the LH surge and HCG administration, the better the PR up to 20 h (P = 0.025); the timing of IUI based on the LH surge was not critical to the achievement of pregnancy within 3 days. In group C, PR improved with the increasing interval between HCG and IUI from <28 h up to 60 h. We conclude that a better PR is achieved if a spontaneous LH surge occurs before HCG administration, especially where the administration of HCG is delayed 8-20 h after an observed LH surge; the timing of IUI based on the LH surge is not critical to the achievement of pregnancy within 3 days.      

A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility

This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility.      

Effect of GnRH antagonists in FSH mildly stimulated intrauterine insemination cycles: a multicentre randomized trial

BACKGROUND: The usefulness of GnRH antagonists in mild controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI) cycles is debated. METHODS: Two-hundred and ninety-nine couples with unexplained or mild male factor infertility were enrolled in this international multicentre randomized controlled trial. Women allocated to the GnRH antagonist group (n=148) received 50 IU recombinant FSH starting on day 3 of the menstrual cycle and Ganirelix 0.25 mg daily starting from the day in which a follicle with a mean diameter of 13-14 mm was visualized at ultrasound. Women allocated to the control group (n=151) were administered only 50 IU recombinant FSH starting on day 3 of the menstrual cycle. Couples were recruited only for their first treatment cycle. The primary outcome was the clinical pregnancy rate per initiated cycle. RESULTS: Baseline characteristics of the two treatment groups were similar. Clinical pregnancy rates per initiated cycle in women who did and did not receive GnRH antagonists were 12.2 and 12.6%, respectively (P=1.00). The relative risk of conception (95% confidence interval) for the use of GnRH antagonists was 1.0 (0.5-1.9). CONCLUSIONS: In mild COH and IUI cycles, any benefit of the use of GnRH antagonists in improving pregnancy rates is <2-fold increase.