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PubMed2003

Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. Current best evidence for the advanced treatment of unexplained subfertility.

When conventional treatment of unexplained infertility has not been successful, the next choice lies between either gonadotrophin treatment with intrauterine insemination (FSH/IUI) and IVF. Cohort studies indicate that FSH/IUI is less effective while the cost per birth is higher with IVF. The relevant evidence should come from randomized controlled trials, but the results need to be recalculated for the outcome of greatest interest, a singleton live birth. Judged by this standard, FSH/IUI is statistically superior to no treatment, but the effect is small in couples with unexplained infertility. By the same standard, IVF is superior to FSH/IUI treatment, but this benefit is achieved only at considerable cost. The evidence is not robust, comprising only a few trials which involve a minute fraction of the existing patients with unexplained infertility. Current best evidence is consistent with a progression from low-tech to high-tech treatment, but it is not convincing enough to support a rigid management protocol. A large multicentre factorial trial is needed to evaluate the relative value of existing empiric treatments for unexplained infertility.

Clomiphene↗
PubMed2003

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.

Clomiphene↗
PubMed2003

Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. Should the guidelines be changed?

The Royal College of Obstetricians and Gynaecologists Guidelines for the management of infertility in secondary care (1998) states that stimulated intrauterine insemination (IUI) has Grade A evidence to confirm its effective use in unexplained infertility. This paper challenges that assertion after closer assessment of the papers upon which it was based. With the current appraisal of the Guidelines as part of the 'scope' of the assessment of infertility management by the National Institute of Clinical Excellence it is important that the guidelines are indeed critically reviewed prior to their updated publication. With the emphasis on minimizing the risk of multiple pregnancies, a formal trial of stimulated IUI is called for in order to justify its continued use in this setting. Strict attention to limiting the number of follicles treated in verified unexplained subfertility is necessary to validate such a trial.

Female↗
PubMed2004

The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI.

INTRODUCTION: Sperm chromatin integrity assessment has been suggested as a fertility predictor. The aim of this study was to examine the relationship between the results of sperm chromatin structure assay (SCSA) and the outcome of IVF, ICSI and intrauterine insemination (IUI). METHODS: A total of 306 consecutive couples undergoing assisted reproduction were included. IUI was performed in 131, IVF in 109 and ICSI in 66. SCSA results were expressed as DNA fractionation index (DFI) and highly DNA stainable (HDS) cell fractions. Reproductive outcome parameters were biochemical pregnancy (BP), clinical pregnancy (CP) and delivery (D). RESULTS: For IUI, the chance of pregnancy/delivery was significantly higher in the group with DFI 27% or HDS >10%. The odds ratios (ORs) (95% confidence intervals) were 20 (2.3-117), 16 (1.9-137) and 14 (1.6-110) for BP, CP and D, respectively. No statistical difference between the outcomes of IVF versus ICSI was observed in the group with DFI 27% group, however, the results of ICSI were significantly better than those of IVF. Comparing ICSI with IVF, the OR (95% CI) for BP was 26 (1.9-350). CONCLUSIONS: SCSA is a useful method for prediction of the outcome of assisted reproduction.

Adult↗
PubMed2004

Posthumous sperm retrieval for the purpose of later insemination or IVF in Israel: an ethical and psychosocial critique.

In October 2003, the Attorney General of the Government of Israel published guidelines allowing posthumous sperm retrieval for the purpose of later insemination or IVF by the surviving female partner. This paper presents an ethical and psycho-social critique of the guidelines, which challenges their basic premise that personal autonomy over-rides any other ethical principle and argues that the autonomy of the adult should not over-ride the well-being of the offspring. It also shows that, despite the centrality of autonomy in the guidelines, they actually infringe on the autonomy of the deceased, and pose challenges to that of the surviving partner. It questions the propriety and very possibility of ascertaining the 'presumed wishes' of the deceased for a posthumous child. Finally, it argues against the document's presentation of posthumous sperm retrieval as a medical procedure and contends that, on the contrary, medicine and science are suborned to the exploitation of the dead.

Cadaver↗
PubMed2004

The effect of human immunodeficiency virus on sperm parameters and the outcome of intrauterine insemination following sperm washing.

BACKGROUND: This is the first study to assess the outcome of sperm washing and intrauterine insemination (IUI) cycles in human immunodeficiency virus-positive (HIV(+)) men to determine any predictors of success, as well as evaluating the effect of HIV on sperm parameters. METHODS: Semen characteristics were evaluated in 106 HIV(+) men and a control group of 234 HIV(-) men, and the effect of markers of HIV disease assessed. Age, stimulation regime, sperm parameters, markers of HIV disease and the use of anti-retrovirals were assessed as predictors of the outcome of sperm washing/IUI cycles in the HIV(+) men. RESULTS: Ejaculate volume, sperm concentration, total count, progressive motility and normal morphology were all significantly higher in the control group compared to the HIV(+) men (P<0.05). A significant positive correlation was observed between CD4 count and sperm concentration, total count, motility, progressive motility type 'a'+'b' and post-preparation concentration and a significant negative correlation with normal sperm morphology of both raw and post-preparation samples. No correlation was observed between viral load (VL), years since diagnosis, use of anti-retrovirals or duration of use and any sperm parameter. The only factors that significantly improved IUI outcome were a VL <1000 copies/ml and the use of anti-retrovirals. CONCLUSIONS: These data demonstrate that sperm parameters are significantly impaired by the presence of HIV infection and in particular correlate with CD4 count. Undetectable VL and the use of anti-retrovirals improve the outcome of IUI/sperm washing in HIV(+) men.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Does ovarian hyperstimulation in intrauterine insemination for cervical factor subfertility improve pregnancy rates?

BACKGROUND: Intrauterine insemination (IUI) can be performed with or without controlled ovarian hyperstimulation (COH). Studies in which the additional benefit of COH on IUI for cervical factor subfertility is assessed are lacking. We assessed whether COH in IUI improved pregnancy rates in cervical factor subfertility. METHODS: We performed a historical cohort study among couples with cervical factor subfertility, treated with IUI. A cervical factor was diagnosed by a well-timed, non-progressive post-coital test with normal semen parameters. We compared ongoing pregnancy rate per cycle in groups treated with IUI with or without COH. We tabulated ongoing pregnancy rates per cycle number and compared the effectiveness of COH by stratified univariable analysis. RESULTS: We included 181 couples who underwent 330 cycles without COH and 417 cycles with COH. Ongoing pregnancy rates in IUI cycles without and with COH were 9.7% and 12.7%, respectively (odds ratio 1.4; 95% confidence interval 0.85-2.2). The pregnancy rates in IUI without COH in cycles 1, 2, 3 and 4 were 14%, 11%, 6% and 15%, respectively. For IUI with COH, these rates were 17%, 15%, 14% and 16%, respectively. CONCLUSIONS: Although our data indicate that COH improves the pregnancy rate over IUI without COH, IUI without COH generates acceptable pregnancy rates in couples with cervical factor subfertility. Since IUI without COH bears no increased risk for multiple pregnancy, this treatment should be seriously considered in couples with cervical factor subfertility.

Adult↗
PubMed2004

Intrauterine insemination versus Fallopian tube sperm perfusion in non-tubal subfertility: a systematic review based on a Cochrane review.

BACKGROUND: The objective of this review was to compare the efficacy of Fallopian tube sperm perfusion (FSP) with intrauterine insemination (IUI) in the treatment of non-tubal subfertility. METHODS: The principles of the Cochrane Menstrual Disorders and Subfertility Group were employed. Only randomized controlled studies comparing FSP with IUI were included in this review. The main outcome measures included live birth rates and pregnancy rates per couple. RESULTS: Twenty-eight studies were found performing the comparison of interest. Overall six studies involving 474 couples were included in the meta-analysis. One study only assessed live birth rates, which resulted in no difference in outcome between FSP and IUI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.39-3.53]. The results in pregnancy rate per couple revealed no statistically significant difference between FSP and IUI (OR 1.76, 95% CI 0.77-4.05). Subgroup analysis revealed that couples suffering from unexplained subfertility clearly benefit from FSP over IUI (OR 2.88, 95% CI 1.73-4.78). Excluding studies which used the Foley catheter for tubal perfusion resulted in a significant difference favouring FSP for all indications (OR 2.42, 95% CI 1.54-3.80). CONCLUSIONS: There is firm evidence that FSP gives rise to higher pregnancy rates in couples with unexplained subfertility and should therefore be advised in these couples. For other indications FSP has not been proven more effective compared with IUI. Results showed that the Foley catheter might not be effective for FSP. Future research should focus on comparing different types of catheters.

Fallopian Tubes↗
PubMed2004

Timing ovulation for intrauterine insemination with a GnRH antagonist.

BACKGROUND: We aimed to assess the efficacy of a GnRH antagonist in intrauterine insemination (IUI) cycles to increase number of mature ovulatory follicles and pregnancy rates. METHODS: Prospective randomized study. Women (18-38 years old) with primary/secondary infertility were included. Eighty-two patients were randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH + GnRH antagonist or rFSH alone. RESULTS: A non-significant increase in the total amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm) was significantly higher in the GnRH antagonist group than in the control group (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly increased in the group of patients receiving the GnRH antagonist (38%) compared to the control group (14%). The only non-single pregnancy (triplets) occurred in the antagonist group. CONCLUSIONS: In this preliminary study, adding the GnRH antagonist to the COS protocol for IUI cycles significantly increased pregnancy rates. Nevertheless, these results may not be associated directly with the antagonist itself but with the fact that more mature ovulatory follicles are present by the day of the hCG. Finally, the risk for multiple gestations needs to be carefully evaluated.

Adolescent↗
PubMed2005

Patients' preferences in deciding between intrauterine insemination and expectant management.

BACKGROUND: Intrauterine insemination (IUI) is a commonly used treatment in subfertile couples. We assessed patients' preferences for IUI relative to expectant management. METHODS: Forty subfertile couples were offered scenarios in which the treatment-independent pregnancy chance was varied against a fixed pregnancy chance after IUI without or with controlled ovarian hyperstimulation (COH) of 8% and 12% per cycle, respectively. The treatment-independent pregnancy chance within 12 months was initially set at 100%, and subsequently reduced until couples switched preferences. We also investigated the impact of the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy on couples' preferences. RESULTS: When pregnancy was guaranteed within a year, all couples would opt for expectant management. Most couples switched to IUI without COH at a 60% chance of a treatment-independent pregnancy and to IUI with COH between a 40% and 60% chance. Where the risk of OHSS was set at 10%, a large majority of the couples preferred expectant management to IUI. At a multiple pregnancy risk of 100%, 77% of the couples would still prefer IUI. CONCLUSIONS: The majority of couples prefer IUI with or without COH when the treatment-independent pregnancy chance in the next 12 months is <50% and <40%, respectively. The risk of a multiple pregnancy does not affect their preference for IUI, whereas IUI is rejected when the risk of OHSS exceeds 10%.

Adult↗
PubMed2005

School-aged children of donor insemination: a study of parents' disclosure patterns.

BACKGROUND: A major concern in relation to donor insemination (DI) is whether children should be told about their genetic origins. This study compared the thoughts, feelings and experiences of DI parents who were inclined towards openness with those who were inclined towards non-disclosure. METHODS: Forty-six families with a 4- to 8-year-old DI-conceived child were interviewed about their decision, their reasons and subsequent concerns regarding disclosure. RESULTS: Thirty-nine percent of parents were inclined towards disclosure whilst the remaining 61% were not. The two main reasons for favouring disclosure were to avoid accidental discovery and a desire for openness. Non-disclosing parents felt that there was no reason to tell and wished to protect family members. The children who had been told reacted with either curiosity or disinterest. CONCLUSIONS: In spite of donor anonymity, parents who were intending to tell their child in the future had optimistic expectations of their child's reaction. Parents who had already told their child generally described the telling experience as a positive one.

Adult↗
PubMed2005

Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study.

BACKGROUND: It was our intention to determine whether hysteroscopic polypectomy before intrauterine insemination (IUI) achieved better pregnancy outcomes than no intervention. METHODS: A total of 215 infertile women from the infertility unit of a university tertiary hospital with ultrasonographically diagnosed endometrial polyps (EP) undergoing IUI were randomly allocated to one of two pretreatment groups using an opaque envelope technique with assignment determined by a random number table. Hysteroscopic polypectomy was performed in the study group. Diagnostic hysteroscopy and polyp biopsy was performed in the control group. RESULTS: Total pregnancy rates and time for success in both groups after four IUI cycles were compared by means of contingency tables and life-table analysis. A total of 93 pregnancies occurred, 64 in the study group and 29 in the control group. Women in the study group had a better possibility of becoming pregnant after polypectomy, with a relative risk of 2.1 (95% confidence interval 1.5-2.9). Pregnancies in the study group were obtained before the first IUI in 65% of cases. CONCLUSIONS: These data suggest that hysteroscopic polypectomy before IUI is an effective measure.

Adult↗
PubMed2005

Solo mothers and their donor insemination infants: follow-up at age 2 years.

BACKGROUND: Findings are presented of the second phase of a longitudinal study of solo-mother families created through donor insemination (DI). METHODS: At the time of the child's second birthday, 21 solo DI mother families were compared with 46 married DI families on standardized interview and questionnaire measures of the psychological well being of the mothers, mother-child relationships and the psychological development of the child. RESULTS: The solo DI mothers showed greater pleasure in their child and lower levels of anger accompanied by a perception of their child as less 'clingy'. Fewer emotional and behavioural difficulties were shown by children of solo than married DI mothers. CONCLUSIONS: The findings from this first cohort of solo DI families to be studied lend further weight to the view that these women represent a distinct subgroup of single parents, who, out of a strong desire for a child, have made the active choice to go it alone. Moreover, this route to parenthood does not necessarily seem to have an adverse effect on mothers' parenting ability or the psychological adjustment of the child.

Child Behavior↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adnexal Diseases↗
PubMed2005

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.

Cohort Studies↗
PubMed2005

Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study.

BACKGROUND: Sperm DNA integrity has been used as a new marker of sperm quality in the prediction of pregnancy. Nevertheless, no previous study has been performed by analysing the same samples that were employed in assisted reproduction. The main objective of this work was to correlate sperm chromatin dispersion (SCD), measured by the SCD test, with semen parameters and pregnancy outcome in intrauterine insemination (IUI). METHODS: A total of 100 semen samples obtained from males of couples undergoing IUI were analysed by the SCD test before and after swim-up, and the results were correlated with semen parameters and pregnancy outcome. RESULTS: SCD was negatively correlated with sperm motility in both ejaculated and processed semen. Sperm recovered by swim-up did not show a significant improvement in DNA integrity. No correlation was found between SCD and pregnancy outcome in IUI. CONCLUSIONS: DNA dispersion, as measured by the SCD test, is not correlated with pregnancy outcome in IUI.

Chromatin↗