Biomedical subjects

P Vandekerckhove

Publications and source records attributed to P Vandekerckhove.

At least 19 recordsLinked to original sources

PubMed2006

Techniques for pelvic surgery in subfertility.

BACKGROUND: Since the introduction of in-vitro fertilisation (IVF) tubal surgery has been less frequently undertaken as a technique to improve fertility in women with damaged fallopian tubes. There are various surgical techniques that can be used to repair blocked or damaged fallopian tubes. OBJECTIVES: To evaluate the role of tubal surgery in the management of tubal infertility and to evaluate surgical techniques for the treatment of tubal infertility. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. We identified relevant trials from the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (searched up to July 2005) and Cochrane Central Register of Controlled Trials (CENTRAL). The following databases were searched using the OVID platform: 1. MEDLINE (1966 to July 2005); 2. EMBASE (1980 to July 2005). SELECTION CRITERIA: All randomised controlled trials investigating the following topics on infertility surgery technique as follows were included.1) The role of infertility surgery versus no treatment.2) The role of infertility surgery versus alternative treatments.3) The role of magnification.4) The role of the CO2 laser at infertility surgery. 5) The role of operative laparoscopy to perform infertility surgery. 6) Any other intervention regarding surgical technique investigated by RCT. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the first two authors. Differences of opinion were recognised and resolved by consensus. Two by two tables were generated for each trial for the dichotomous outcome of pregnancy and the effects on pregnancy rate of each study is expressed as an odds ratio with 95% confidence intervals. MAIN RESULTS: Seven randomised control trials were identified. No RCTs comparing infertility surgery versus no treatment or alternative treatments were found. There was no RCT found investigating the use of magnification for tubal surgery. There was no evidence for or against the use of a CO2 laser compared with standard techniques for adhesiolysis (OR for pregnancy 1.07, 95% CI 0.40 to 2.87) or salpingostomy (OR for pregnancy 1.38, 95% CI 0.47 to 4.05) from two RCTs. One RCT randomised women for salpingostomatolysis by laparotomy and laparoscopy using the classic approach or the one suture technique. There was no evidence of benefit or disadvantage when laparoscopy was compared to laparotomy. The OR for bilateral tubal patency was 1.32 (95% CI 0.55 to 3.22) and unilateral tubal patency OR was 0.82 (95% CI 0.29 to 2.29). The pregnancy rate was not reported. There was no evidence of benefit or disadvantage from two RCTs assessing the use of a prosthesis at salpingostomy compared with non-use (combined odds of pregnancy (term) in group using the prosthesis as compared to the control (OR for pregnancy at term 1.17, 95% CI 0.47 to 2.93). There was no evidence of benefit or disadvantage difference in one RCT comparing Cuff versus Bruhat technique for salpingostomy One RCT compared two methods of salpingostomy (OR for pregnancy rate ( intrauterine) 1.02, 95% CI 0.22 to 4.61). One RCT showed no evidence of benefit or disadvantage for the use of thermocoagulation or electrocoagulation at adhesiolysis, odds for pregnancy rate between the two groups OR 0.87 (95% CI 0.51 to 1.46). AUTHORS' CONCLUSIONS: From these limited data there is no evidence of benefit or disadvantage of tubal surgery versus no treatment or alternative treatments. Likewise there is no evidence of advantage or disadvantage of using microsurgery over standard techniques; laparoscopic approach over laparotomy; the use of CO2 laser; or electrocoagulation over thermocoagulation. Randomised controlled trials should be undertaken to determine the role of tubal surgery versus no treatment or alternative treatments. Randomised controlled trials should be undertaken to determine the role at tubal surgery of magnification, laparoscopic approach, the use of lasers or electrocoagulation.

Fallopian Tube Diseases↗

PubMed2006

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion formation and adhesion reformation. Since subsequent fertility is reduced with increasing severity of periadnexal adhesions, pelvic adhesions will remain a clinical problem in infertility patients. Steroids, antihistamines and heparin were amongst the first substances to be advocated for adhesion prevention. More recently icodextrin 4%, hyaluronic acid agents and SprayGel have been used. This review aims to evaluate the role of fluid and pharmacological agents in the prevention of adhesions in fertility-conserving gynaecological surgery. OBJECTIVES: To investigate fluid and pharmacological agents for adhesion prevention when used as adjuvants during pelvic surgery. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. The following databases were searched: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. SELECTION CRITERIA: Randomised controlled trials investigating the use of fluid and pharmacological agents to prevent adhesion formation after fertility-conserving gynaecological surgery. DATA COLLECTION AND ANALYSIS: Data extraction and analysis was performed independently by two authors (Metwally M and Watson A). Two-by-two tables were generated for dichotomous outcomes and expressed as odds ratios (OR) with 95% confidence intervals (CI). For continuous outcomes a standardised mean difference was used. MAIN RESULTS: There is no evidence of benefit from the use of steroids, dextran or other pharmacological agents in any of the outcomes. The use of hyaluronic acid agents may decrease adhesion formation (OR 0.31, 95% CI 0.19 to 0.51) and prevent the deterioration of pre-existing adhesions (OR 0.28 (95% CI 0.12 to 0.66). There is insufficient evidence for the use of icodextrin 4% or SprayGel as adhesion-preventing agents. None of the studied agents has been shown to improve the pregnancy rate when used as an adjunct during pelvic surgery. AUTHORS' CONCLUSIONS: The current evidence for the use of fluid and pharmacological agents for the prevention of adhesions is limited. There is no evidence on any benefit for improving pregnancy outcomes when pharmacological and fluid agents are used as an adjunct during pelvic surgery. There is insufficient evidence for the use of the following agents: steroids, icodextrin 4%, SprayGel and dextran in improving adhesions following surgery. There is some evidence that hyaluronic acid agents may decrease the proportion of adhesions and prevent the deterioration of pre existing adhesions. However, due to the limited number of studies available, this evidence should be interpreted with caution and further studies are needed.

Anticoagulants↗

PubMed2005

Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection was the first established treatment for anovulatory PCOS patients but was largely abandoned due to the risk of post-surgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have an over-production of follicles and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Moreover ovulation induction with gonadotrophins, though effective, is an expensive, inconvenient and time-consuming treatment requiring intensive monitoring. Surgical therapy with laparoscopic ovarian "drilling" (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their use. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, and/or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH STRATEGY: We used the search strategy of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS that undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: Fifteen trials were identified and six were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost. MAIN RESULTS: There was no evidence of a difference in live births or ongoing pregnancies between LOD and gonadotrophins and the pooled Odds Ratio (OR) (all studies) was 1.04 (95% CI 0.74, 1.99) and 1.16 (95% CI 0.72, 1.86) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% vs 16%, OR: 0.13, 95% CI: 0.03 to 0.59). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 955% 0.36, 1.86). AUTHORS' CONCLUSIONS: There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long term effects of LOD on ovarian function.

Anovulation↗

PubMed2005

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent fertility outcomes in couples with infertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 2 March 2004), MEDLINE (1966 to Mar 2004), EMBASE (1980 to Mar 2004), Biological Abstract (1980 to Mar 2004) and reference lists of articles. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eleven randomised controlled trials were identified and included in this review. All trials were assessed for quality criteria. The studied primary outcome was live birth (and ongoing pregnancy), with secondary outcomes pregnancy, miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention (three trials including 381 participants) was associated with a significant increase in the odds of live birth (Peto OR 2.98, 95%CI 1.40 to 6.37) and of pregnancy (Peto OR 3.30, 95%CI 2.00 to 5.43). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. For the comparison of tubal flushing with oil-soluble media versus tubal flushing with water-soluble media (six trials including 1,483 participants), the increase in the odds of live birth for tubal flushing with oil-soluble versus water-soluble media (Peto OR 1.49, 95%CI 1.05 to 2.11) was based on two trials where statistical heterogeneity was present and the higher quality trial showed no significant difference; there was no evidence of a significant difference in the odds of pregnancy (Peto OR 1.24, 95%CI 0.97 to 1.57). The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone; three trials including 555 participants) showed no evidence of a significant difference in the odds of pregnancy (Peto OR 1.18, 95%CI 0.82 to 1.70) or live birth (Peto OR 1.06, 95%CI 0.64 to 1.77). Adverse event data were only available for the comparison OSCM versus WSCM: OSCM carried a significantly higher chance of intravasation (Peto OR 5.41, 95%CI 2.57 to 11.37) but a significantly lower chance of immediate pain (Peto OR 0.53, 95%CI 0.34 to 0.84), prolonged pain (Peto OR 0.26, 95%CI 0.15 to 0.45) and post-procedure bleeding (Peto OR 0.22, 95%CI 0.15 to 0.31), and no serious adverse events were reported. AUTHORS' CONCLUSIONS: There is evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy and live birth versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing water-soluble media versus no intervention, would be a useful further guide to clinical practice. Further research is merited to ascertain the mechanism of the fertility enhancing effect of oil-soluble media, as to whether this is a 'tubal flushing' phenomenon, an effect on the intraperitoneal environment, or an implantation enhancing effect on the endometrium.

Contrast Media↗

PubMed2005

Cancer cell dissemination during curative surgery for colorectal liver metastases.

AIM: The amount of cancer cells disseminated during curative surgery for colorectal liver metastases (CRLM) may be responsible for recurrence. Haematogenous and intrahepatic cancer cell dissemination was evaluated, and its impact on cancer recurrence was assessed. METHOD: Twenty patients with resectable CRLM were included in a prospective study. Twelve patients underwent curative resection for 21 metastases. Ten selected metastases in eight patients were treated with radiofrequency ablation (RFA) followed by resection at the same operative session. Cancer cell dissemination was determined before, during and after surgery using 'real time' quantitative RT-PCR assay, based on detection and quantification of CEA and CK20 mRNA transcripts. RESULTS: Circulating cancer cells were detected in 80% and intrahepatic cancer cells in 37% of the patients, though without impact on cancer recurrence. The amounts of disseminated cancer cells were significantly increased after surgery. This increase was similar in patients treated with and without RFA. RFA caused complete tumour destruction. CONCLUSION: Curative surgery for CRLM significantly increases the amount of disseminated cancer cells. Radiofrequency ablation can completely destroy selected resectable CRLM without excessive cancer cell dissemination. Neither haematogenous nor intrahepatic cancer cell dissemination were related to cancer recurrence in this small patient series.

Aged↗

PubMed2003

Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma.

BACKGROUND: Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone. OBJECTIVE: This study was aimed to explore the effect of exogenously administered progesterone in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA or physiologic saline (Sal). Medroxyprogesterone acetate or placebo was instilled daily into the oesophagus before and during the inhalatory OVA challenge phase. RESULTS: Progesterone worsened allergic airway inflammation in OVA-challenged mice, as evidenced by enhanced bronchial responsiveness to inhaled metacholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher bronchial and systemic IL-5 levels in the progesterone group. The ratio of IL-4/IFN-gamma levels in bronchoalveolar lavage fluid and numbers of eosinophil colony-forming units in the bone marrow were also elevated in the latter group. Progesterone, however, did not influence allergen-specific IgE production, nor did it affect bronchial responses in Sal-challenged mice. CONCLUSION: Our data show that exogenously administered progesterone aggravates the phenotype of eosinophilic airway inflammation in mice by enhancing systemic IL-5 production. Progesterone also increases bronchial hyper-reactivity.

Animals↗

PubMed2003

Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions.

BACKGROUND: We previously developed a real-time quantitative RT-PCR technique to detect breast carcinoma cells in peripheral blood (PB). The aim of the current study was to improve cytokeratin 19 (CK19) quantification using plasmid dilutions of cloned PCR fragments to obtain a more reliable and reproducible quantification of CK19 transcripts. MATERIALS AND METHODS: PB samples of 14 stage IV breast cancer patients and 23 healthy controls were examined with RT-PCR using plasmid quantification. RESULTS: Median CK19+ copy numbers of one and 11 were detected in the control group and stage IV breast cancer patients, respectively (Mann-Whitney, P </=0.0001). When comparing the results obtained using cell line dilutions with those obtained using plasmid dilutions, a good correlation was observed (r(2) = 0.98). CONCLUSIONS: Plasmid dilutions are more reliable than cell line dilutions for quantification of gene expression, and more objective criteria for positivity could be defined based on the characteristics of the standard curve (slope and intercept). A more universally accepted agreement on the definition of the cut-off value for positivity is needed.

Breast Neoplasms↗

PubMed2002

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy outcomes in couples with infertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group and a recent search of electronic databases completed in December 2001 was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eight randomised controlled trials were identified and included in this review. A further one randomised controlled trial is ongoing. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth (and ongoing pregnancy), miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention was associated with a significant increase in the odds of pregnancy (OR 3.57, 95%CI 1.76-7.23). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. Tubal flushing with oil-soluble media was associated with a significant increase in the odds of live birth versus tubal flushing with water-soluble media (OR 1.49, 95%CI 1.05-2.11) but the odds of pregnancy showed no significant difference (OR 1.23, 95%CI 0.95-1.60) and there was evidence of statistical heterogeneity for these two outcomes. The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone) showed no significant difference in the odds of pregnancy (OR 1.16, 95%CI 0.78-1.70) or live birth (OR 1.06, 95%CI 0.64-1.77). REVIEWER'S CONCLUSIONS: There is some evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing each versus no intervention, are required to provide convincing evidence as to whether the technique should be accepted into widespread clinical practice.

Contrast Media↗

PubMed2002

Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia.

PCR-based monitoring of minimal residual disease (MRD) in acute leukemias can be achieved via detection of fusion gene transcripts of chromosome aberrations or detection of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements. We wished to assess whether both PCR targets are complementary in acute myeloid leukemia (AML). We investigated 105 consecutive AML cases for the presence of fusion gene transcripts by reverse transcriptase polymerase chain reaction (RT-PCR): AML1-ETO associated with t(8;21), CBFB-MYH11 with inv(16), PML-RARA with t(15;17), BCR-ABL with t(9;22), and MLL-AF4 with t(4;11). In 17 out of 105 AML cases (16%), fusion gene transcripts were found. Ninety-five of these AML patients (13 with fusion gene transcripts) were also investigated for the presence of IGH, IGK, TCRG and TCRD rearrangements by Southern blot and/or PCR heteroduplex analysis and sequencing. In nine out of 95 patients (9.5%), such rearrangements were found. Combined data revealed that only one patient with a fusion gene transcript had a coexistent Ig/TCR rearrangement. The nine AML patients with Ig/TCR rearrangements, as well as five additional AML patients from a previous study were investigated in more detail, revealing that Ig/TCR rearrangements in AML are immature and unusual. The presence of Ig/TCR rearrangements in AML did not correlate with RAG gene expression levels as determined by real-time quantitative PCR. In conclusion, fusion gene transcripts and Ig/TCR rearrangements are infrequent, but complementary MRD-PCR targets in AML.

Acute Disease↗

PubMed2001

Surgery or embolisation for varicocele in subfertile men.

BACKGROUND: A varicocele is an, almost exclusively left-sided, varicosity of the pampiniform plexus of the spermatic cord, forming a tangle of distended blood vessels in the scrotum. Although the concept that varicocele causes male subfertility and therefore varicocelectomy cures male subfertility has been around for almost fifty years now, the mechanisms by which varicocele would affect fertility have not yet been satisfactorily explained, and neither have the mechanisms by which varicocelectomy would resolve subfertility. Furthermore, it has been questioned whether a causal relation exists at all between the distension of the pampiniform plexus and impairment of fertility. OBJECTIVES: To evaluate the effect of varicocele treatment on pregnancy rate in subfertile couples. SEARCH STRATEGY: Relevant trials were identified in the Cochrane Menstrual Disorders and Subfertility Group's specialised register of controlled trials. A MEDLINE search, using the group's search strategy, was performed for the period 1966-2000. Also, hand searching was performed of 22 specialist journals in the field from their first issue till 2000. Cross references and references from review articles were checked. SELECTION CRITERIA: RCTs were included if they were relevant to the clinical question posed, if they reported pregnancy rates as an outcome measure, and if they reported data in treated (surgical ligation or radiological embolization of the internal spermatic vein) and untreated groups. DATA COLLECTION AND ANALYSIS: Six studies met the inclusion criteria for this review. One (Nieschlag 1995/1998) was an extension of a previously published study (Nieschlag 1995/1998), which left five studies for analysis (Nilsson 1979; Breznik 1993; Madgar 1995; Yamamoto 1996; Nieschlag 1995/1998). The results of a WHO megatrial are awaited but as yet are unavailable. The WHO data will be added if and when they will have become available. All five only included men from couples with subfertility problems, one (Madgar 1995) excluded men with sperm counts <5 mill/mL, three (Nilsson 1979; Breznik 1993; Yamamoto 1996) also included men with normal semen analysis. One study (Yamamoto 1996) specifically addressed only men with subclinical varicoceles as diagnosed by thermography. Potentially relevant trials were screened independently by two authors (JE and JC). Any differences of opinion were resolved by consensus meeting (none occurred for this review). Studies were excluded from meta-analysis if they made comparisons other than those specified above. MAIN RESULTS: One trial (Madgar 1995) reported a statistically significant improvement in pregnancy rate following high ligation of the left spermatic vein. None of the other four studies showed individually a significant effect on pregnancy rates of varicocele treatment over no-treatment (Nilsson 1979; Breznik 1993; Yamamoto 1996), or over counseling only (Nieschlag 1995/1998). The combined RR (Relative Risk; random effects method) of the five studies is 1.06 (95%CI 0.57-1.94), the Peto OR (Odds Ratio) is 1.15 (95%CI 0.73-1.83). REVIEWER'S CONCLUSIONS: Insufficient evidence exists that treatment of varicocele in men from couples with otherwise unexplained subfertility does improve the couple's spontaneous pregnancy chances.

Embolization, Therapeutic↗

PubMed2000

Bromocriptine for unexplained subfertility in women.

BACKGROUND: Bromocriptine improves hyperprolactinemic amenorrhea and so could also be helpful in the treatment of unexplained subfertility in women. OBJECTIVES: To assess the effects of bromocriptine in women with unexplained subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: Randomised trials comparing bromocriptine with placebo or no treatment in women with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Two reviewers applied the eligibility criteria and assessed trial quality independently. MAIN RESULTS: Three trials involving of 127 women were included. All trials were double-blind comparisons with placebo, and one was of crossover design. Conception rates with bromocriptine treatment did not improve compared with placebo (odds ratio was 1.12, 95% confidence interval 0.48 to 2.57). REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate bromocriptine use in women with unexplained subfertility. However trials for women with unexplained subfertility who also have expressible galactorrhea may be worthwhile.

Bromocriptine↗

PubMed2000

Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea.

BACKGROUND: The administration of clomiphene citrate is followed by an enhanced release of pituitary gonadotropins resulting in follicular recruitment. After the drug is stopped, there is continuing secretion of estradiol, selection of the dominant follicle and, in successful cases, ovulation. Clomiphene is indicated as the initial treatment in the majority of women with amenorrhoea and oligomennorhoea. In women with irregular ovulation it seems to re-establish typical frequency of ovulation. Its effectiveness in oligo-amenorrhoeic women was tested in a number of randomized controlled trials at that time. These trials form the basis for the following review. OBJECTIVES: Clomiphene citrate enhances the release of pituitary hormones, often resulting in ovulation. The objective of this review was to assess the effects of clomiphene citrate on ovulation and pregnancy in women with oligo-ovulatory subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: Randomised trials of clomiphene compared with placebo or no treatment in women with oligo-ovulatory subfertility of at least 12 months duration. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Four studies were included. They were all of crossover design. Since it was not possible to separate data from the first and second phases of these trials, the effect of clomiphene may be overestimated. Compared with placebo, clomiphene citrate was associated with increased ovulation. The odds ratio for high doses (50-250 milligrams per day) was 6.82 (95% confidence interval 3.92 to 11.85). This dropped to a non-significant odds ratio of 1.29 (95% confidence interval 0.48 to 3.49) with low doses (10 milligrams per day). Clomiphene citrate (all doses) was associated with an increased pregnancy rate per treatment cycle (odds ratio 3.41, 95% confidence interval 4.23 to 9.48). REVIEWER'S CONCLUSIONS: Clomiphene citrate (at doses between 50 to 250 milligrams per day) appears to be an effective method of inducing ovulation and improving fertility in oligo-ovulatory women. However adverse effects include possible ovarian cancer risk and risk of multiple pregnancy.

Amenorrhea↗

PubMed2000

Clomiphene citrate for unexplained subfertility in women.

OBJECTIVES: Clomiphene citrate appears to increase ovulation in women with oligo-ovulatory subfertility. It may also work in women with unexplained subfertility, perhaps by correcting an unidentifiable ovulatory dysfunction. The objective of this review was to assess the effects of clomiphene citrate in women with unexplained subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of clomiphene citrate (doses of 50 to 250 milligrams per day up to 10 days) compared to placebo or no treatment in women with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Five studies were included. Four trials were of crossover design, and quality of the randomisation was variable. Compared to placebo, clomiphene citrate was associated with an increase in pregnancy rates. The odds ratio for pregnancy per patient was 2.38 (95% confidence interval 1.22 to 4.62). The odds ratio of pregnancy per cycle was 2.5 (95% confidence interval 1.35 to 4.62). REVIEWER'S CONCLUSIONS: Clomiphene citrate appears to modestly improve pregnancy rates in women with unexplained subfertility. However adverse effects include a possible ovarian cancer risk and risk of multiple pregnancy.

Clomiphene↗

PubMed2000

Danazol for unexplained infertilty.

BACKGROUND: The androgen, Danazol, was developed in the 1970's as a treatment for endometriosis. Its use was soon advocated in women with unexplained infertility. Two randomized trials were subsequently conducted to assess the effectiveness of danazol in this population. OBJECTIVES: The objective of this review was to assess the effects of danazol on pregnancy rates in women with unexplained subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: Randomised trials of danazol compared with placebo or no treatment in women with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. MAIN RESULTS: Two trials involving 68 women were involved. There was no difference found in pregnancy rate between danazol and placebo (odds ratio 2.57, 95% confidence 0.53 to 12.46). REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the effect of danazol on pregnancy rates in women with unexplained subfertility. The need to use contraception during danazol treatment, adverse effects and costs are additional considerations.

Danazol↗

PubMed2000

Ovulation induction with urinary follicle stimulating hormone versus human menopausal gonadotropin for clomiphene-resistant polycystic ovary syndrome.

BACKGROUND: The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in women with clomiphene resistance WHO group 2 dysfunction undergoing ovulation induction as well as the risk of spontaneous abortion if conception takes place. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotropin (hMG). Ovulation induction in women with clomiphene resistant WHO group 2 dysfunction who often have clinical features of polycystic ovarian syndrome (PCOS), is a major challenge. The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in this population. There also appears to be an increased risk of spontaneous abortion in those who conceive, perhaps associated with elevated LH levels. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotrophins. OBJECTIVES: To determine the effectiveness of daily FSH versus daily hMG in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of rates of pregnancy and moderate to severe ovarian hyperstimulation syndrome (OHSS). SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: All RCTs relevant to the clinical question were selected. DATA COLLECTION AND ANALYSIS: A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. MAIN RESULTS: No significant benefit was demonstrated from semi-purified FSH versus hMG in terms of pregnancy rate: common odds ratio per patient 0.66 (95% CI 0.35-1.24) and per cycle 0.89 (95% CI 0.51-1.53). FSH appeared to be associated with a reduction in moderate to severe OHSS: common odds ratios 0.2 (95% CI 0.09-0.46). REVIEWER'S CONCLUSIONS: In women with PCOS, no significant difference could be demonstrated between FSH and hMG, in terms of pregnancy rate. However, given similar cost, potential advantages in terms of purity and a possible reduction in OHSS risk, highly purified or recombinant FSH are likely to be widely adopted in the future. Further research should consider live birth as a primary clinical outcome, given concerns over the association between high androgen and LH levels with spontaneous abortion risk.

Clomiphene↗

PubMed2000

Oil-soluble versus water-soluble media for assessing tubal patency with hysterosalpingography or laparoscopy in subfertile women.

BACKGROUND: There has been debate in the literature for more than 40 years as to whether flushing of the Fallopian tubes enhances fertility and whether this presumed therapeutic effect is greater with oil-soluble media than with water-soluble media. A meta-analysis of the therapeutic role of oil-soluble contrast media at hysterosalpingography was published in March 1994 (Watson 1994). This Cochrane Review is an expansion and update of that overview. OBJECTIVES: To evaluate the effect of flushing the Fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy rates in infertility patients. SEARCH STRATEGY: 1. For randomised controlled trials (RCTs): we searched the Cochrane Subfertility Review Group specialised register of controlled trials. 2. For non-randomised controlled studies: Medline and manual search of eight relevant journals. SELECTION CRITERIA: Six RCTs and six non-randomised controlled studies. In two studies tubal flushing was compared with no treatment-controls. Eleven studies, comprising a total of 2635 subjects, compared oil- with water-soluble media. DATA COLLECTION AND ANALYSIS: Independently by first 2 authors for: 1. Methodological trial characteristics 2. Characteristics of participants 3. OUTCOMES: the main studied outcome was pregnancy rate per patient MAIN RESULTS: In comparison with no treatment, a significant benefit on pregnancy rates was seen by flushing the tubes with oil-soluble media (OR 1.80, 95% CI 1.29-2.50) but not with water-soluble media (OR 0.87, 95% CI 0.50-1.52). In the direct comparison of oil- and water-soluble media the former lead to significantly higher pregnancy rates (OR 1.92, 95% CI 1.60-2.29). The treatment effect appeared similar in RCTs and non-RCTs. Subgroup analysis suggested the therapeutic benefit was greatest for patients suffering from unexplained infertility and least for those with tubal factor infertility. REVIEWER'S CONCLUSIONS: Flushing of the tubes with oil-soluble media increases subsequent pregnancy rates in infertility patients. The hypothesis that tubal "plugs" are a cause of proximal tubal occlusion and that oil-soluble media may flush them out, is supported by new techniques such as falloposcopy. Clinicians should consider flushing the tubes with OSCM before contemplating more invasive therapies.

Contrast Media↗

PubMed2000

Gonadotrophin-releasing hormone analogue as an adjunct to gonadotropin therapy for clomiphene-resistant polycystic ovarian syndrome.

BACKGROUND: Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin releasing hormone analogue (GnRHa) used prior to human menopausal gonadotropin (hMG/FSH) administration may improve the outcome of ovulation induction. OBJECTIVES: To assess if GnRHa pre-treatment plus FSH/hMG increase the rate of clinical pregnancy and/or decrease the rate of spontaneous abortion in women with WHO group 2 ovulatory dysfunction, compared with hMG/FSH alone. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: All relevant published and unpublished RCTs were selected. Three RCTs were identified comparing these two approaches. DATA COLLECTION AND ANALYSIS DATA EXTRACTION: A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. MAIN RESULTS: Studies were clinically and statistically homogenous. Common odds ratios for pregnancy per treatment cycle and moderate to severe ovarian hyperstimulation syndrome (OHSS) were 1.50 (0.72-3.12) and 1.40 (0.5-3.92) respectively. REVIEWER'S CONCLUSIONS: These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.

Clomiphene↗

PubMed2000

Androgens versus placebo or no treatment for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. Androgens have been suggested as a treatment because its binding proteins maintain a maintain a high intratesticular level testosterone essential for spermatogenesis and because the epididymis and seminal vesicles affect the seminal constitution and sperm motility and are also androgen-dependent. However exogenous testosterone was found to exert negative feedback on the pituitary-gonadal axis and thereby to suppress FSH and LH secretion. Spermatogenesis was thus adversely affected. Nevertheless androgens are used for the treatment of male infertility either for a putative direct "stimulatory" or "rebound" therapy. The stimulatory androgens used are mesterolone and testosterone undecanoate which, it is postulated, in a form and dosage that does not influence pituitary gonadotrophin secretion, either have a direct stimulatory effect on spermatogenesis or influence sperm transport and maturation though an effect on the epididymis, ductus deferens and seminal vesicles. Other androgens have been used to produce a rebound effect. These androgens are administered to suppress gonadotrophin secretion and spermatogenesis. After androgen therapy is discontinued there is a surge of FSH and LH and spermatogenesis is recommenced. Because of their different proposed mechanisms of action, stimulatory and rebound androgen therapy are analysed separately in the comparisons. This review considers the available evidence of the effect of androgens for idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective of this review was to assess the effect of androgen treatment of men among couples where failure to conceive has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of mesterolone or testosterone undecanoate versus placebo or no treatment (stimulatory therapy), or testosterone enanthate or testosterone undecanoate versus placebo or no treatment (rebound therapy) in couples where subfertility is attributed to male factor. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. MAIN RESULTS: Eleven trials involving 930 patients were included. For stimulatory therapy, androgens had little effect on endocrinal outcomes and sperm parameters. The rate of pregnancy after androgens with stimulatory effect compared to no treatment or placebo was also similar (odds ratio 1.10, 95% confidence interval 0.75 to 1.61). In rebound therapy, no difference was found in sperm parameters. The pregnancy rate after androgens with rebound effect also showed no difference compared to no treatment or placebo (odds ratio 1.60, 95% confidence interval 0.42 to 6.16). Adverse effects such as headaches and exanthema were reported. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of androgens for male subfertility. [This abstract has been prepared centrally.]

Androgens↗