Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: a comparison with basal markers for ovarian reserve

BACKGROUND: The aim of this study was to investigate the predictive accuracy and clinical value of performing either a single or a repeated clomiphene citrate challenge test (CCCT) in predicting poor response in IVF, compared to that of currently used basal ovarian reserve markers. METHODS: Sixty-three patients undergoing their first IVF treatment were prospectively included. After measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were measured on day 10 (cd10). A second CCCT was performed after a washout period of one cycle. In all patients the tests were followed by an IVF treatment. Poor response (<4 oocytes or cancellation due to impaired (<3 follicles) or absent follicular growth) was used as primary outcome measure. RESULTS: Both the single as well as the repeated CCCT markers had a rather good discriminative potential for the prediction of poor response (area under the receiver operating characteristic curve (ROCAUC): FSH cd10=0.79, inhibin B cd10=0.79, mean FSH cd10=0.82 and mean inhibin B cd10=0.88). This compared well with the performance of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC 0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a better discriminating potential for the prediction of poor response (ROCAUC 0.92). At a specificity level of approximately 0.97, sensitivity and the positive predictive value were marginally improved in the CCCT models. CONCLUSIONS: Performing a CCCT (single or repeated) has a rather good ability to predict poor response in IVF. However, it appears that the predictive accuracy and clinical value of the CCCT is not clearly better than that of basal FSH in combination with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF should not be advocated.     

The effects of clomiphene citrate upon ovulation and endocrinology when administered to patients with unexplained infertility

Twenty-four couples with unexplained infertility were studied in a spontaneous cycle followed by a clomiphene citrate (CC) cycle (150 mg, days 5-9). All spontaneous cycles were ovulatory, as defined by follicular collapse determined by transvaginal sonography. In CC cycles, 6/24 (25%) cycles demonstrated luteinized unruptured follicles (LUF). In 2/6 LUF cycles there was no apparent luteinizing hormone (LH) surge. LUF cycles had significantly elevated LH levels in the follicular phase compared to ovulatory CC cycles. There was no apparent difference in serum oestradiol. In CC cycles multifollicular development occurred in 87.5% of cycles, with significantly elevated serum oestradiol. Luteinizing hormone and follicle-stimulating hormone were elevated in the follicular phase compared to spontaneous cycles. This study suggests a high incidence of LUF when CC is administered to ovulatory patients, and its use in patients with ovulatory infertility is questioned.     

Luteinized unruptured follicle syndrome: incidence and recurrence rate in infertile women with unexplained infertility undergoing intrauterine insemination

BACKGROUND: The objective of this study was to determine the incidence and recurrence rate of luteinized unruptured follicle (LUF) syndrome in women with unexplained infertility undergoing intrauterine insemination (IUI). METHODS: A total of 167 women with unexplained infertility who underwent 292 cycles of IUI were enrolled in the study. All patients were treated with clomiphene citrate, 50-150 mg/daily from day 5 to 9 of their menstrual cycle. Ultrasound examination to confirm ovulation was performed on the day of IUI (day 0) and every day thereafter for another 3 days (days 1, 2 and 3). A total of 69 women who failed to conceive in the first cycle and 56 women who failed to conceive in the second cycle underwent second and third cycles, respectively. RESULTS: Of the total 167 patients who underwent first cycle, 42 (25%) had LUF. The incidence of LUF was 56.5% in 69 patients who underwent a second cycle of IUI treatment, of whom 33 patients had LUF in the first cycle with recurrence rate of 78.6%. In 56 patients who underwent 3 consecutive cycles, the incidence of LUF was 58.9% and recurrence rate of 90%. No pregnancies were recorded in patients with LUF during the study period. CONCLUSION: The incidence and recurrence rate of LUF are significantly increased in subsequent cycles of IUI. In these patients, other options of infertility treatment might be justified.     

Cancer and male infertility: Gamete intra-Fallopian transfer or in-vitro fertilization after failed ovarian stimulation and intrauterine insemination in unexplained infertility?

A prospective randomized study was designed to compare gameteintra-Fallopian transfer (GIFT) and in-vitro fertilization (IVF)and embryo transfer in the treatment of couples who have failedto conceive after at least three cycles of ovarian stimulationand intrauterine insemination (IUI). A total of 69 couples withprimary unexplained infertility of at least 2 years' durationplus at least three failed cycles of ovarian stimulation andIUI were randomly allocated to either GIFT or IVF/embryo transfer.The clinical pregnancy rate was 34% after GIFT treatment and50% after IVF/embryo transfer. This difference was not statisticallysignificant. The twin rate in the IVF/embryo transfer groupwas higher than in the GIFT group (53 versus 17%, P = 0.005).We conclude that patients with unexplained infertility and failedovarian stimulation and IUI can still achieve encouraging pregnancyrates with IVF/embryo transfer or GIFT. Since IVF/embryo transferis the least invasive of the two procedures and may yield diagnosticinformation, we would favour this therapy; however, the numberof embryos transferred should be reduced to two to reduce therisk of twin pregnancy.     

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.     

Antral follicle count and FSH concentration after clomiphene citrate challenge test in the prediction of ovarian response during IVF treatment

BACKGROUND: We compared: (i) antral follicle count (AFC) in the early follicular phase, after the clomiphene citrate challenge test (CCCT) and before ovarian stimulation following pituitary down-regulation; and (ii) age of women, body mass index, basal and stimulated serum FSH concentrations and AFC in predicting the ovarian response of infertile women aged <40 years with basal FSH <10 IU/l on recruitment in their first IVF cycle. METHODS: Two months prior to the treatment cycle, AFC and basal FSH concentration were determined on day 2-3 of a spontaneous period and on day 10 after CCCT. All women received a standard stimulation regimen. Ovarian response was represented by the number of oocytes, serum estradiol, the duration and dosage of gonadotrophins. RESULTS: There was no significant difference between basal, stimulated and down-regulated AFC. AFC achieved the best predictive value in relation to the number of oocytes, followed by combined FSH concentration (sum of the two FSH concentrations) and age of women. Both basal AFC and combined FSH concentration were predictive factors of serum estradiol concentration, whereas stimulated FSH concentration was predictive of the total dosage of gonadotrophins. CONCLUSION: Combined FSH concentration after CCCT provides additional information in predicting ovarian response.     

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.     

The effectiveness of IVF in unexplained infertility: a systematic Cochrane review. 2002,

BACKGROUND: IVF is an accepted treatment for unexplained infertility. The objective of this review was to determine whether, for unexplained infertility, IVF improves the probability of live birth compared with: (i) expectant management; (ii) clomiphene citrate (CC); (iii) intrauterine insemination (IUI); (iv) IUI with controlled ovarian stimulation; and (v) gamete intra-Fallopian transfer (GIFT). METHODS: This was based on a Cochrane review. Randomized controlled trials (RCTs) which compared the effectiveness of IVF with expectant management, CC, IUI with or without controlled ovarian stimulation and GIFT were included. Patients included couples with unexplained infertility. Live birth rate per woman/couple was the main outcome measure. RESULTS: Nine RCT were identified. Five RCTs were included in the final meta-analysis. There were no comparative data for CC and live birth rates for expectant management or GIFT. There was no significant difference in clinical pregnancy rates between IVF and expectant management. There was no evidence of a difference in live birth rates between IVF and IUI either without (OR 1.96, 95% CI 0.88 to 4.36) or with (OR 1.15, 95% CI 0.55 to 2.42) ovarian stimulation. Clinical pregnancy rates with IVF were significantly higher compared with GIFT (OR 2.14, 95% CI 1.08 to 4.22) as were the multiple pregnancy rates (OR 6.25, 95% CI 1.70 to 23.00). Clinical heterogeneity was present among the studies. There was no evidence of statistical heterogeneity. CONCLUSIONS: The effectiveness of IVF in unexplained infertility remains unproven. Larger trials with adequate power are warranted.     

Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH

BACKGROUND: The study was conducted to compare the results of intrauterine donor insemination (DI) under ovarian stimulation with either clomiphene citrate (CC), in a fixed protocol, or FSH, with ovarian monitoring. METHODS: Forty-nine patients were randomized using a computer-generated list to receive highly purified urinary FSH (starting dose of 150 IU) and were subjected to periodic vaginal ultrasound and estradiol determinations. HCG was given when > or =2 follicles (> or =17 mm) were identified and estradiol reached >400 pg/ml. Intrauterine insemination (IUI) was performed 36 h later. The other 51 received CC on a fixed protocol (100 mg/day from the day 5-10 of the ovarian cycle) with HCG being administered on the day 12, and IUI performed 36 h later. Up to six IUI cycles were performed on all patients if pregnancy was not reached before. Women failing to conceive in the CC group underwent IUI with FSH. The main outcome measures were intrauterine gestational sac observed by transvaginal ultrasound, per cycle and per woman pregnancy rate (PR) and multiple PR. RESULTS: The per cycle PR was significantly higher in the FSH group, 14.4% (30/209) versus 6.1% (16/261), as well as the per woman PR, 61.2% (30/49) versus 31.4% (16/51). 12.5% (2/16) of pregnancies obtained in the CC group were multiple, compared with 20% (6/30) in the FSH group. There were no triplets or higher order pregnancies in CC versus two in FSH (6.7% of pregnancies). Patients failing to conceive with CC, who later underwent intrauterine DI with FSH, had similar results to the primary FSH group: 54.3% PR per patient (19/35) and 16.0% per cycle (19/118), with a multiple PR of 31.6% (6/19). The PR for women starting with CC cycles and, if pregnancy was not obtained, continuing with six FSH cycles, was 69.2%. CONCLUSIONS: The PR obtained with CC stimulation was approximately half that obtained with FSH. There was a trend to lower multiple PR with CC. It is recommended that each case should be considered on an individual basis and the treatment options discussed with patients. In our opinion, CC could be a reasonable approach for young women with good prognosis, whereas in the remaining cases FSH would be the preferable method.     

Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility

The aim of this prospective randomized controlled study wasto determine the possible role of ovulation induction with intrauterineinsemination (IUI) in the treatment of unexplained infertility.A total of 100 patients were randomized to receive ovulationinduction with or without IUI. All patients were treated withlong-course gonadotrophinreleasing hormone analogue (GnRHa),starting in the luteal phase, and exogenous follicle stimulatinghormone (FSH) to induce follicular growth. Ovulation was inducedusing human chorionic gonadotrophin and timed intercourse (TI)was advised 24–48 h later or IUI was effected 36—48h later. Both the cycle fecundities (21.8 and 8.5%) and thecumulative ongoing pregnancy rates after three cycles (42 and20%) were significantly higher (P < 0.03) in the IUI groupthan in the TI group respectively. This is a clear indicationthat ovulation induction with IUI is an effective treatmentmethod for unexplained infertility, but ovulation inductionwith TI has a negligible impact in this large group of patients.     

Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility

BACKGROUND: Adding clomiphene citrate (CC) to FSH for controlled ovarian stimulation (COS) decreases FSH dose required for optimum stimulation. However, because of its anti-estrogenic effects, CC may be associated with lower pregnancy rates offsetting the FSH-dose reduction benefit. Previously, we reported the success of aromatase inhibition in inducing ovulation without antiestrogenic effects. METHODS: A prospective pilot study that included women with unexplained infertility undergoing COS and intrauterine insemination. Thirty-six women received the aromatase inhibitor letrozole + FSH, 18 women received CC + FSH and 56 women received FSH only. Each woman received one treatment regimen in one treatment cycle. All patients were given recombinant or highly purified FSH (50-150 IU/day) starting on day 3 to 7 until day of hCG. RESULTS: The FSH dose needed was significantly lower in letrozole + FSH and CC + FSH groups compared with FSH-only without a difference in number of follicles >1.8 cm. Pregnancy rate was 19.1% in the letrozole + FSH group, 10.5% in the CC + FSH group and 18.7% in the FSH-only group. Both pregnancy rate and endometrial thickness were significantly lower in CC + FSH group compared with the other two groups. Estradiol (E2) levels were significantly lower in the letrozole + FSH group compared with the other two groups. CONCLUSIONS: Similar to CC, aromatase inhibition with letrozole reduces FSH dose required for COS without the undesirable antiestrogenic effects sometimes seen with CC.     

The value of intrauterine insemination with washed husband's sperm in the treatment of infertility

Twenty-nine infertile couples were treated by intrauterine insemination(IUI)of washed sperm from a sub-fertile husband (n = 16), incases of gynaecological (n = 3), combined (n = 4) or idiopathic(n = 6) infertility; 116 treatment cycles redted in 11 ongoingpregnancies. Between 0.25 and 0.45 ml of capacitation medium,containing at least 500 000 pretreated spermatozoa, were inseminated.Pretreatment of first split fractions was performed by centrifugationand swimming up of motile spermatozoa. The pregnancy per cycleindex (P/C) for IUI was 9.5% for a total of 37.9% of all couplestreated achieving pregnancy. These results suggest a substantialbenefit compared with a calculated six months' cumulative pregnancyrate of 4.2% independent of treatment, for this infertile population.The value of IUI in selected cam of infertility seems obviousbut needs further investigation.     

腹腔镜联合人工授精治疗子宫内膜异位症不孕的临床观察

目的探讨子宫内膜异位症（EMs）不孕患者腹腔镜术后行夫精人工授精妊娠率的影响因素。方法回顾性分析164例腹腔镜术后的EMs不孕患者进行的318个人工授精周期的临床资料。以年龄、不孕年限、腹腔镜术后时间、用药情况、周期数、是否促排卵、r-AFS分期、IUI时机分别进行妊娠率的比较。结果 EMs不孕患者术后人工授精的周期妊娠率为13.21%。年龄≤35岁的周期妊娠率高于35岁以上者（χ2=6.687,P〈0.05）,不孕年限≤5年的妊娠率高于5年以上者（χ2=5.430,P〈0.05）,腹腔镜术后1年内行人工授精的妊娠率高于1年以上者（χ2=6.005,P〈0.05）,Ⅰ～Ⅱ期患者的妊娠率高于Ⅲ～Ⅳ期患者（χ2=8.264,P〈0.05）,加用促排卵治疗的妊娠率高于自然周期者（χ2=4.569,P〈0.05）,3周期内人工授精的妊娠率高于3周期以上者（χ2=4.031,P〈0.05）,双次IUI者妊娠率高于单次者（χ2=4.371,P〈0.05）,差异均有统计学意义。而术后是否使用GnRH-a则与妊娠率无关。结论 EMs不孕患者腹腔镜术后行人工授精治疗的最佳时间是术后1年内3周期内有较高的妊娠率,建议同时加用促排卵治疗。     

Clomiphene citrate does not affect the secretion of alpha3, alphaV and beta1 integrin molecules during the implantation window in patients with unexplained infertility.

BACKGROUND: The expression of integrin molecules on the endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. A prospective, controlled study was carried out to investigate the effect of clomiphene citrate (CC) on secretions of beta1, alpha3 and alphaV integrin molecules in the endometrium of patients with unexplained infertility during the implantation window. METHODS: A total of 40 endometrial samples was evaluated in both spontaneous (n = 13) and ensuing clomiphene-treated cycles (100 mg on days 5-9) and also from fertile women serving as controls (n = 14) during postovulatory 7th or 8th day of menstrual cycle. A semiquantitative grading system (H-score) was used to compare the immunohistochemical staining intensities. Endometrial thickness and serum oestradiol and progesterone concentrations were also measured on the day of sampling. RESULTS: Staining of alpha(v) but not beta1 and alpha3 integrins was significantly less intense in infertile cases than fertile control cases (1.42 +/- 0.12 versus 2.21 +/- 0.13 respectively, P = 0.012) and this was not restored to normal concentrations with treatment. CONCLUSIONS: Our study indicated that cc treatment significantly decreased the endometrial thickness and increased oestradiol and progesterone concentrations. However, secretion of alpha(v), beta1 and alpha3 integrin molecules, which might play a role in implantation, was not affected.     

Evaluation of intrauterine insemination with washed spermatozoa from the husband in the treatment of infertility.

In this study, we examined the efficacy of intrauterine insemination with washed spermatozoa from the husband (AIH/IUI) in the treatment of infertility. A total of 127 treatment cycles were completed (1.95 cycles per patient). The indications for AIH/IUI were male subfertility (group I: 53 couples), cervical factor (group II: four couples), male and cervical factor (group III: six couples) and unexplained infertility (group IV: two couples). Sperm washing caused a reduction of the sperm concentration from 52 x 10(6)/ml to 44 x 10(6)/ml (P less than 0.08) and motility from 49% to 45% (P less than 0.03). Twelve pregnancies were achieved (18.5% per couple and 9.5% per cycle): eight pregnancies in group I (15.1%), one in group II (25%) and three in group III (50%). Of the 12 pregnancies, eight occurred in the first insemination cycle, three in the second and one in the third (1.4 cycles/pregnancy). Sperm motility was significantly higher in the pregnant than in the non-pregnant group (65.5% versus 46.4%, respectively; P less than 0.004), whereas no significant difference was observed in the sperm concentration between these two groups (39 x 10(6)/ml and 54 x 10(6)/ml, respectively). In conclusion, AIH/IUI is a technically easy and non-invasive procedure which offers a satisfactory pregnancy rate in selected couples with male subfertility and/or cervical factor infertility.     

子宫内膜微创术及宫腔内人工授精治疗不明原因不孕的疗效观察

目的观察子宫内膜微创术及宫腔内人工授精治疗不明原因不孕患者的疗效。方法选择2008年3月至2009年9月因不明原因不孕在不孕不育门诊就诊的患者108例。所有患者均进行过3次及以上正规宫腔内人工授精未孕。以上患者随机分为研究组47例,对照组61例。研究组于月经周期第8-10天行子宫内膜微创术,用5号刮匙酌情轻微搔刮子宫内膜壁,当周期于卵泡成熟破裂前后行IUI。对照组仅行IUI。结果研究组47例共进行82周期治疗,对照组61例共进行125周期治疗,研究组临床妊娠率20.73%,累积妊娠率36.17%。对照组妊娠率12%,累积妊娠率24.59%。结论子宫内膜微创术联合IUI治疗,可明显提高不明原因不孕患者的妊娠率,无毒副作用,易于操作,值得基层推广应用。     

Endometriosis-associated infertility: double intrauterine insemination improves fecundity in patients positive for antiendometrial antibodies

Citation
Subit M, Gantt P, Broce M, Seybold DJ, Randall G. Endometriosis‐associated infertility: double intrauterine insemination improves fecundity in patients positive for antiendometrial antibodies. Am J Reprod Immunol 2011; 66: 100–107 Problem Prospective registry study evaluating effects of endometriosis (E) and serum antiendometrial antibodies (AEA) on fecundity in intrauterine insemination (IUI) cycles. Method of study AEA assays on 572 consecutive women receiving 969 single and 274 double IUI cycles. Logistic regression was utilized. Results Fecundity was 11.5% (143/1243 cycles). Double IUI improved fecundity with significance achieved in certain study groups. Compared to the AEA? subgroup, all study groups except for the E+ AEA? group had significantly lower fecundity. Two study groups receiving double IUI had significantly increased fecundity, E? AEA+ (OR: 5.1, CI: 1.1–22.7, P = 0.032) and E+ AEA+ (OR: 4.1, CI: 1.2–14.0, P = 0.025) and significant predictors of pregnancy (E? AEA+, OR: 7.8, CI: 1.7–36.2, P = 0.009 and E+ AEA+, OR: 4.2, CI: 1.2–15.1, P = 0.026). Conclusion Double IUI improves fecundity in AEA+ patients. E‐associated infertility is better diagnosed by the AEA assay than by surgery. Double IUI should be attempted prior to assisted reproductive technologies in AEA+ patients with normal fallopian tubes.     

A randomized trial between GIFT and ovarian stimulation for the treatment of unexplained infertility and failed artificial insemination by donor.

This study was designed to investigate the surplus effect of gamete intra-Fallopian transfer (GIFT) over ovarian stimulation alone, in patients with unexplained infertility. A total of 50 patients with unexplained infertility of at least 3 years duration, or unexplained failure of artificial insemination by donor (AID) for at least 12 cycles, meeting strict inclusion criteria, were randomly selected for either two GIFT cycles or two ovarian stimulation cycles. Ovarian stimulation was combined with timed intercourse, or timed cervical donor insemination. In 38 completed GIFT cycles, five clinical pregnancies (13.2% per cycle) occurred and in 44 ovarian stimulation cycles four clinical pregnancies occurred (9.1% per cycle). Five remaining GIFT cycles were converted into in-vitro fertilization leading to two pregnancies. Of the 50 patients suffering from unexplained infertility, the 23 who did not have AID gave rise to four pregnancies out of 39 cycles (10.3%); from the remaining 27 patients who underwent AID, seven pregnancies were achieved out of 48 cycles (14.6%). No statistical differences between GIFT and ovarian stimulation treatment were found. Therefore, the GIFT success rates can be explained at least in part, if not fully, by the effect of ovarian stimulation alone. Consequently, ovarian stimulation should be considered in unexplained infertility before more elaborate forms of assisted reproduction are used.     

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.     

Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome

A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.