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.     

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.     

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.     

Controlled ovarian hyperstimulation: a state of neutrophil activation

PROBLEM: To investigate if controlled ovarian hyperstimulation (COH) affects the expression of neutrophil adhesion molecules and if a correlation exists between neutrophil activation and serum sex-steroid levels. METHOD OF STUDY: The pilot study was carried out in the in vitro fertilization (IVF) unit of our department, and required no modification of our routine IVF protocol. Four patients arriving for baseline hormonal profile on day 1 of the menstrual cycle before initiation of COH (control group) and 11 patients admitted for oocyte recovery (study group) were included. Venous blood was obtained from all patients and examined for hormonal profile and neutrophil activation. The latter was performed by staining for the surface adhesion molecules beta2 integrin and L-selectin. Positive cell count and mean fluorescence intensity were determined by flow cytometry. RESULTS: While neutrophil L-selectin was significantly lower in the study group than in the control group, neutrophil beta2 integrin was nonsignificantly higher. Though no significant correlations were found between neutrophil adhesion molecules and patient age, serum estradiol level, and human chorionic gonadotropin level; neutrophil L-selectin was negatively correlated with serum progesterone levels. CONCLUSIONS: COH leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for promoting fertility and preventing complications of COH.     

GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages

BACKGROUND: The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use. METHODS: Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection. RESULTS: The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005). CONCLUSIONS: A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.     

Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study

BACKGROUND: Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles. Nitric oxide, formed in vivo from L-arginine, may play a key role in follicular maturation and ovulation. METHODS: To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation, 37 IVF patients were divided into two groups according to ovarian stimulation protocols: group I, GnRH agonist plus pure (p)FSH plus oral L-arginine (n = 18); and group II, GnRH agonist plus pFSH plus placebo (n = 19). Hormonal, ultrasonographic and Doppler evaluations were performed, and plasma and follicular fluid nitrite/nitrate concentrations were monitored. RESULTS: Thirty-two patients completed the study. In group I (n = 16), plasma L-arginine concentrations increased from (basal) 87 +/- 12 micromol to 279 +/- 31 micromol (P = 0.002) on the day of beta-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles > or =17mm was lower (P = 0.038) in group I than group II. The "good quality" embryos were fewer in number (P = 0.034) and pregnancy rate, both per patient (P = 0.024) and per embryo transfer (P = 0.019), was lower in group I. In the L-arginine group, an increased follicular fluid concentration of nitrite/nitrate was observed. On day 8 of the cycle, elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries. Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality (r = -0.613; P = 0.005) and perifollicular artery pulsatility index (r = -0.609; P = 0.021). CONCLUSIONS: L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles.     

应用r-hFSH促排卵并行宫腔内人工授精治疗多囊卵巢综合征不孕症

目的探讨多囊卵巢综合征(PCOS)不孕症的治疗方法.方法先行对症治疗,比如抑制LH、雄激素的高水平分泌,恢复月经等.再用r-hFSH进行促排卵并行宫腔内人工授精(IUI)治疗.结果治疗30例,93周期,妊娠19例,总妊娠率为63.3%;周期妊娠率为20.4%,其中双胞胎8例,3胞胎1例,流产1例.娩出婴儿均健康正常.结论应用r-hFSH促排卵并行IUI治疗PCOS不孕症有较好疗效.     

Interleukin-2 and ovarian hyperstimulation syndrome: a pilot study

A prospective case-controlled study was conducted to evaluatethe association between the concentrations of interleukin-2(IL-2) in human follicular fluid obtained at the time of oocytecollection for in-vitro fertilization (IVF) and the developmentof ovarian hyperstimulation syndrome (OHSS). Follicular fluidwas obtained at the time of oocyte collection for IVF consecutivelyfrom 40 patients at risk of developing OHSS. Among the 40 patientsparticipating in the study, seven subsequently developed OHSS.Their follicular fluid samples, together with those of an additionalseven patients matched by age who did not develop OHSS, weretested for osmolality, total protein content and IL-2 concentrations,and mean serum oestradiol concentrations at the time of humanchorionic gonadotrophin (HCG) administration and the mean numberof aspirated oocytes were also measured. Follicular fluid IL-2concentrations were significantly higher (P < 0.002) in theOHSS group as compared to the control group. No significantdifferences were found between the two groups regarding themean serum oestradiol concentration on the day of HCG administration,or the mean number of aspirated oocytes, follicular fluid osmolality,or total protein concentrations. This study suggests an associationbetween follicular fluid IL-2 concentration and OHSS. IL-2 isknown to cause ‘vascular leak syndrome’, which resemblesOHSS. These observations, together with the established interactionbetween the immune and the reproductive systems, may suggesta pivotal role of IL-2 in the pathogenesis of OHSS.     

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.      

Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET

This study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 ± 0.3 IU/l (mean±SEM), 6.0 ± 0.3 IU/l, and 8.2 ± 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 ± 0.6, 10.2 ± 0.6, and 7.9 ± 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate.     

Pregnancy outcome and ovarian antibodies in infertility patients undergoing controlled ovarian hyperstimulation

PROBLEM: Several endocrine markers are well-established, but not absolute, predictors of successful outcomes following controlled ovarian hyperstimulation. Another potential predictor for success may be a marker of ovarian autoimmunity. Ovarian antibodies (OVAB) are detected in women with unexplained infertility. We tested the hypothesis that women with OVAB have a poorer pregnancy outcome in in vitro fertilization (IVF). METHOD OF STUDY: Serum samples (n = 47) were assessed by a previously described immunoassay for OVAB in a cross-sectional, retrospective study design. RESULTS: Women who became pregnant had a lower frequency of OVAB than women who did not become pregnant (25.0% [4/16] vs. 58.1% [18/31], respectively; P = 0.03). There was no significant difference in day 3 estradiol, amount of human menopausal gonadotropin given, peak estradiol, the number of follicles observed, or the number of eggs retrieved between women who achieved pregnancy and those who did not. CONCLUSIONS: Together with other information such as reproductive hormone levels and measures of follicle growth, OVAB may contribute additional information for prediction of successful IVF outcomes.     

Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study

BACKGROUND: Intravenous albumin administration has been described for many years as a debatable, but probably useful preventive measure in ovarian hyperstimulation syndrome (OHSS). The present study details the largest randomized controlled trial to date of albumin infusion versus no treatment in IVF patients with a high risk of developing moderate to severe OHSS. METHODS: Between March 1999 and February 2002, women undergoing IVF at the IVI Valencia with >20 retrieved oocytes were included. A total of 988 patients was initially enrolled. Immediately after oocyte retrieval, patients were allocated to two groups based on a computer randomization: the first group received 40 g human albumin; the second group received no treatment. Subjects were weighed and a blood analysis performed immediately after oocyte retrieval and again 7 days later. Women were monitored on an outpatient basis until menstruation, or until fetal heart activity was detected. Twelve subjects were excluded due to follow-up loss, leaving 976 women (377 of them oocyte donors), with 488 in each group. RESULTS: No difference was found between the two groups in terms of patient characteristics and outcome. Moderate-severe and severe-only OHSS rates were similar. The incidence of haemoconcentration and liver and renal dysfunction at 7 days after oocyte retrieval was similar in the two groups. In women who developed moderate/severe (n = 66) or only severe (n = 46) OHSS, there was no difference based on prior albumin administration between blood parameters or body weight on the day of oocyte retrieval, 7 days later, and even when comparing variation between both measurements. Moreover, the number of patients with paracentesis, hospital admissions, complications and days of OHSS until resolution did not differ. CONCLUSIONS: Albumin infusion on the day of oocyte retrieval is not a useful means of preventing the development of moderate-severe OHSS.     

Further considerations on natural or mild hyperstimulation cycles for intrauterine insemination treatment: effects on pregnancy and multiple pregnancy rates

BACKGROUND: The high iatrogenic multiple pregnancy rate associated with intrauterine insemination (IUI) in hyperstimulated cycles is becoming less acceptable. Therefore we investigated data from an earlier prospective trial with regard to the specific question of whether the application of mild hyperstimulation in IUI cycles could be an alternative strategy for obtaining acceptable pregnancy rates while preventing a high multiple pregnancy rate, compared with natural cycles for IUI. METHODS: Pregnancy outcome of 310 natural and 334 mildly hyperstimulated cycles for IUI in 171 couples with unexplained or mild male factor subfertility was analysed on a patient level with random coefficient models. RESULTS: Pregnancy rates were similar: 35 and 39.8% per couple in the natural and mildly hyperstimulated cycles respectively (P = 0.60). Multiple pregnancies, all twin pregnancies, were conceived significantly more frequently in the mild hyperstimulation group (27% of the pregnancies) than in the natural cycle group (4% of the pregnancies) (P = 0.01). All multiple pregnancies in the hyperstimulation group were conceived in multifollicular cycles. Multifollicular development was strongly associated with the application of mild hyperstimulation only (odds ratio 21.14, 95% confidence interval 8.15-54.79). CONCLUSION: The application of a mild hyperstimulation protocol as an alternative to a standard hyperstimulation protocol for IUI does not result in higher pregnancy rates than IUI in the natural cycle, while at the same time multiple pregnancies cannot be avoided. Therefore, there is no place for the use of gonadotrophins in IUI treatment.     

Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study

BACKGROUND: We aimed to investigate whether sperm DNA quality may predict intrauterine insemination (IUI) outcome. METHODS: The study was designed in a prospective cohort fashion, at a tertiary centre for reproductive medicine. A total of 119 patients underwent 154 cycles of IUI. Parameters related to demography, cycle management and semen sample used for IUI were evaluated. Conventional semen parameters, morphology (strict criteria), sperm DNA fragmentation and stability [evaluated by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and acridine orange staining under both acid and acid + heat denaturing conditions respectively] were measured. The main outcome measure was clinical pregnancy, defined as ultrasonographic visualization of intrauterine gestational sac(s). RESULTS: Logistic regression analyses were done on six sets of data, including all cycles combined, cycles with washed samples, first cycle of each couple, first cycle of each couple with washed samples, cycles stimulated with gonadotrophins and finally gonadotrophin-stimulated cycles with washed samples. The number of pre-ovulatory follicles on day of hCG, the age of the woman and the percentage of sperm with acid- + heat-resistant DNA were the parameters that predicted IUI outcome in most of these data subsets. For the gonadotrophin-stimulated cycles, age of the man appeared as a predictor as opposed to that of the woman; and for the cycles within this subgroup, where the semen sample was washed, sperm DNA fragmentation and age of the man were the only two parameters to predict IUI outcome. No samples with >12% of sperm having DNA fragmentation resulted in pregnancy. CONCLUSIONS: The number of follicles, age of the woman/man and sperm DNA quality may predict IUI outcome.     

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.     

C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for IVF cycle

BACKGROUND: The aim of the present study was to determine serum and follicular fluid C-reactive protein (CRP) levels in patients undergoing controlled ovarian hyperstimulation (COH) for IVF-embryo transfer cycle, and their possible correlation to COH variables. PATIENTS AND METHODS: The subjects were 16 consecutive patients undergoing our routine IVF long GnRH agonist protocol. Blood was drawn three times during the COH cycle: (i) the day on which adequate suppression was obtained (Day-S); (ii) the day of, or prior to HCG administration (Day-HCG); and (iii) the day of (and before) oocyte pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid CRP were compared among the three time points. Serum and follicular fluid CRP were measured with a commercial immunoturbidimetric assay. RESULTS: Serum levels of CRP were significantly higher on Day-OPU and Day-HCG than on Day-S, and significantly higher on Day-OPU than on Day-HCG. No difference was observed between follicular and serum CRP levels on Day-OPU. No significant correlations were found between serum and follicular fluid CRP, or between serum CRP-to-BMI ratio and serum sex steroid levels or IVF treatment variables. CONCLUSIONS: The significant increase in serum CRP levels during COH, especially after HCG administration, suggests that COH potentiates a state of systemic inflammation.     

Febrile morbidity in severe and critical ovarian hyperstimulation syndrome: a multicentre study

The objective of this study was to define the incidence of febrile morbidity and its causes in severe and critical ovarian hyperstimulation syndrome (OHSS). For this purpose, we reviewed the medical records of all OHSS patients hospitalized in 16 out of 19 tertiary medical centres in Israel between January 1987 and December 1996. Febrile morbidity was defined as at least one episode of temperature rise above 38 degrees C lasting > or =24 h. A total of 2902 patients (3305 hospitalizations) with OHSS was identified, of whom 196 had severe, and 13 critical, OHSS. Among the 209 patients investigated the incidence of febrile morbidity was 82.3%, of which 20.5% was attributed to urinary tract infection, 3.8% to pneumonia, 3.3% to upper respiratory tract infection, 2.0% to intravenous line phlebitis, 1.0% to cellulitis at an abdominal puncture site, 1.0% to postoperative wound infections and 0.5 % to gluteal abscess at the site of progesterone injection. Non-typical organisms were frequently isolated, such as Pseudomonas, Proteus, Klebsiella and Enterobacter species. No infectious aetiology was found in 105 patients (50.2%). Hypoglobulinaemia was recorded in most patients, while ascitic and pleural fluids aspirated from these patients contained high globulin concentrations. We conclude that infection-related febrile morbidity in severe and critical OHSS is high, and may be attributed to some degree of immunodeficiency associated with loss of plasma globulins to the third space. However, non-infection-related febrile morbidity is even higher and may be attributed to endogenous pyrogenic mechanisms.      

C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for IVF cycle

Hum. Reprod.,      

The role of laparoscopy in intrauterine insemination: a prospective randomized reallocation study

BACKGROUND: We questioned whether a laparoscopy should be performed after a normal hysterosalpingography before starting intrauterine inseminations (IUI) in order to detect further pelvic pathology and whether a postponed procedure after six unsuccessful cycles of IUI yields a higher number of abnormal findings. METHODS: In a randomized controlled trial, the accuracy of a standard laparoscopy prior to IUI was compared with a laparoscopy performed after six unsuccessful cycles of IUI. The major end-point was the number of diagnostic laparoscopies revealing pelvic pathology with consequence for further treatment such as laparoscopic surgical intervention, IVF or secondary surgery. Patients were couples with medical grounds for IUI such as idiopathic subfertility, mild male infertility and cervical hostility. RESULTS: Seventy-seven patients were randomized into the diagnostic laparoscopy first (DLSF) group and the same number was randomized into the IUI first (IUIF) group. The laparoscopy was performed on 64 patients in the DLSF group, 10 patients withdrew their consent from participation and three patients (3%) became pregnant prior to laparoscopy. In the IUIF group, 23 patients remained for laparoscopy because pregnancy did not occur after six cycles of IUI. From the original 77 randomized patients, 38 patients became pregnant and 16 patients dropped out. Abnormal findings during laparoscopy with therapeutic consequences were the same in both groups: in the DLSF group, 31 cases (48%) versus 13 cases (56%) in the IUIF group, P = 0.63; odds ratio (OR) = 1.4; 95% confidence interval (CI): 0.5-3.6. The ongoing pregnancy rate in the DLSF group was 34 out of 77 patients (44%) versus 38 out of 77 patients (49%) in the IUIF group (P = 0.63; OR = 1.2; 95% CI: 0.7-2.3). CONCLUSIONS:Laparoscopy performed after six cycles of unsuccessful IUI did not detect more abnormalities with clinical consequences compared with those performed prior to IUI treatment. Our data suggest that the impact of the detection and the laparoscopic treatment of observed pelvic pathology prior to IUI seems negligible in terms of IUI outcome. Therefore, we seriously question the value of routinely performing a diagnostic and/or therapeutic laparoscopy prior to IUI treatment. Further prospective studies could be performed to determine the effect of laparoscopic interventions on the success rate of IUI treatment in order to rule out completely the laparoscopy from the diagnostic route prior to IUI.     

The significance of the ionophore-challenged acrosome reaction in the prediction of successful outcome of controlled ovarian stimulation and intrauterine insemination

BACKGROUND: This prospective study compared the acrosome reaction following ionophore challenge (ARIC) versus conventional sperm parameters and sperm velocities in predicting successful outcome following ovarian stimulation and intrauterine insemination. METHODS: All patients were offered a maximum of three treatment cycles. Conventional semen analysis was performed and sperm velocities were measured using computer-aided sperm analysis. Acrosome-reacted sperm were stained using chlortetracycline after ionophore challenge. Multiple logistic regression analysis and the receiver-operator characteristic curve analysis were applied to determine the best predictive variables and their cut-off values. RESULTS: ARIC score was the most significant variable in predicting pregnancy, followed by the percentage of induced acrosome-reacted sperm, serum estradiol levels on the day of hCG and sperm morphology by strict criteria. Higher spontaneous acrosome reaction had a negative relationship with pregnancy. ARIC score of 10% had a sensitivity of 85.3% and a specificity of 85.5%. The positive and negative predictive values were 64.2 and 96.6% respectively and the false positive and negative rates were 14.7 and 14.5% respectively. CONCLUSION: ARIC score was a better predictor of pregnancy than conventional sperm parameters and sperm velocities.