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Biomedical subjects

M J Heineman

Publications and source records attributed to M J Heineman.

At least 19 recordsLinked to original sources

[Subfertility in overweight women].

The prevalence of overweight individuals in The Netherlands is increasing sharply as has also been observed in populations worldwide. In addition to the long-term health risks of being overweight, overweight women of reproductive age are more commonly faced with reproductive disorders. Women who are overweight are less fertile than women of normal weight. The chances of both spontaneous conception and conception after ovulation induction and assisted reproduction are lower in women who are overweight. The chance of a live birth is also decreased due to an increased risk of miscarriage. Furthermore pregnancy outcome is compromised by obesity-related complications of pregnancy. Weight loss of 5-15% in subfertile women who are overweight increases the chance of spontaneous conception and conception after fertility treatment and can be achieved through a low-calorie diet, increased exercise and behaviour modification.

Female↗

Intra-uterine insemination for unexplained subfertility.

BACKGROUND: Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates. OBJECTIVES: To determine whether for couples with unexplained subfertility IUI improves the live birth rate compared with timed intercourse (TI), both with and without ovarian hyperstimulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorder and Subfertility Group Trials Register (searched March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), SCIsearch and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. SELECTION CRITERIA: Truly randomised controlled trials (RCTs) with at least one of the following comparisons were included: --IUI versus TI, both in a natural cycle; --IUI versus TI, both in a stimulated cycle; --IUI in a natural cycle versus IUI in a stimulated cycle; --IUI with OH versus TI in natural cycle; --IUI in a natural cycle versus TI with OH. Only couples with unexplained subfertility were included. DATA COLLECTION AND ANALYSIS: Quality assessment and data extraction were performed independently by two review authors. Outcomes were extracted and the data were pooled. Subgroup analyses and sensitivity analyses were done where possible. MAIN RESULTS: In the six trials where IUI was compared with TI, both in stimulated cycles, there was evidence of an increased chance of pregnancy (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50). A significant increase in pregnancy rate was also found for women where IUI with OH was compared with IUI in a natural cycle (three RCTs, 415 women: OR 2.33, 95% CI 1.46 to 3.71). However, the trials provided insufficient data to investigate the impact of IUI with or without OH on several important outcomes including live birth, multiple pregnancies, miscarriage and risk of ovarian hyperstimulation. There was no evidence of a difference in pregnancy rate for IUI with OH compared with TI in a natural cycle (one RCT, 51 women: OR 4.05, 95% CI 0.39 to 41.87). No RCTs were found for the other two comparisons. AUTHORS' CONCLUSIONS: There is evidence that IUI with OH increases the live birth rate compared to IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared to TI both in stimulated cycles. There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. Therefore, couples should be fully informed about the risks of IUI and OH as well as alternative treatment options.

Female↗

Cumulative pregnancy rates after three cycles of minimal stimulation IVF and results according to subfertility diagnosis: a multicentre cohort study.

BACKGROUND: In minimal stimulation IVF, treatment is aimed at using the single oocyte that spontaneously develops to dominance. To prevent untimely ovulation, a GnRH antagonist is administered in the late follicular phase of the natural cycle together with recombinant FSH for substitution. Owing to the lack of ovarian stimulation, minimal stimulation IVF is a low-risk and patient-friendly treatment. In this study, effectiveness of minimal stimulation IVF was studied. METHODS: In this prospective multicentre cohort study, minimal stimulation IVF was offered to 350 patients. All indications for conventional IVF were included. Main outcome measures were pregnancy rates per cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 336 patients completed 844 cycles (2.5 per patient). The overall ongoing pregnancy rate per started cycle was 8.3% [95% confidence interval (CI) 6.4-10.2%]. The cumulative ongoing pregnancy rate after up to three cycles was 20.8% (95% CI 16.4-25.3%) per patient. No differences were found according to indication for IVF. CONCLUSIONS: Minimal stimulation IVF seems suitable for all indications studied. Pregnancy rates are encouraging. Owing to the low-risk and patient-friendly nature of this protocol, it seems a feasible treatment option for patients requiring IVF.

Adult↗

Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection.

BACKGROUND: In both in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), selection of the most competent embryo(s) for transfer is generally based on morphological criteria. However, many women fail to achieve a pregnancy after transfer of good quality embryos. One of the presumed causes is that such morphologically normal embryos show an abnormal number of chromosomes (aneuploidies). In preimplantation genetic screening (PGS), embryos are analysed for aneuploidies and only embryos that are euploid for the chromosomes tested are transferred. This technique has been suggested and used to improve pregnancy rates for the following indications: (i) advanced maternal age, (ii) repeated IVF failure, (iii) repeated miscarriage and (iv) testicular sperm extraction (TESE)-ICSI. Although PGS is used more and more often, its effectiveness is still unclear. OBJECTIVES: To assess the effectiveness of PGS in terms of live births in women undergoing IVF or ICSI treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2005), MEDLINE (1966 to present) and EMBASE (1980 to present) (searched March 2005) and reference lists of articles. We also contacted authors for providing additional data when necessary. SELECTION CRITERIA: Trials for all four suggested indications as mentioned above were sought. All relevant published randomised controlled trials were selected. They were eligible for inclusion if the comparison dealt with IVF/ICSI with PGS versus IVF/ICSI without PGS. DATA COLLECTION AND ANALYSIS: Relevant data were extracted independently by two authors. All trials were screened and analysed according to predetermined quality criteria. Validity was assessed in terms of method of randomisation, completeness of follow-up, intention-to-treat analysis and presence or absence of blinding. The primary outcome measure was live birth rate per woman. Secondary outcome measures were the proportion of women reaching embryo transfer, mean number of embryos transferred per transfer, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, ongoing pregnancy rate, proportion of women reaching embryo transfer after cryopreservation and proportion of women whose child has a congenital malformation. MAIN RESULTS: Two randomised controlled trials met our predetermined eligibility criteria. These trials used PGS for advanced maternal age. The primary outcome of live birth rate per woman was not significantly different in the PGS and control groups, though data were only available from one study. The live birth rate was 11% (21 out of 199) in the PGS group, versus 15% (29 out of 190) in the control group (OR 0.65; 95% CI 0.36 to 1.19). For a control group rate of 15%, these data suggest a live birth rate using PGS of between 4% and 17%. Ongoing pregnancy rate was provided in both studies. This was not significantly different with a combined odds ratio of 0.64 (95% CI 0.37 to 1.09). For a control group rate of 20%, this suggests an ongoing pregnancy rate using PGS of between 8% and 21%. AUTHORS' CONCLUSIONS: To date there is insufficient data to determine whether PGS is an effective intervention in IVF/ICSI for improving live birth rates. Available data on PGS for advanced maternal age showed no difference in live birth rate and ongoing pregnancy rate. However, only two randomised trials were found, of which one included only 39 patients. For both studies comments on their methodological quality can be made. Therefore more properly conducted randomised controlled trials are needed. Until such trials have been performed PGS should not be used in routine patient care.

Aneuploidy↗

Monocyte activation, but not granulocyte activation, is inhibited in the presence of developing ovarian follicles.

This study was set up to evaluate the influence of ovarian factors on the acute phase of the endotoxin-induced glomerular inflammatory reaction. Six groups of rats with permanent jugular vein cannulas were used. This included three groups with increased progesterone and/or 17beta-oestradiol concentrations (day 14 pregnant rats, pseudopregnant rats and lactating rats), one group with the presence of developing ovarian follicles (cyclic rats), and two groups with both increased sex hormone concentrations and the presence of developing ovarian follicles (day 14 pregnant rats treated with FSH and day 21 pregnant rats). Rats were infused for 1h with either saline or endotoxin (1 microg/kg body weight) and sacrificed 4h after the infusion. Kidney sections were snap-frozen and prepared for immunohistochemistry. Endotoxin-induced glomerular granulocyte infiltration was increased only in the groups of rats with increased progesterone and/or 17beta-oestradiol concentrations. This could be due to endotoxin-induced ICAM-1 and/or VCAM-1 expression, which was observed in all endotoxin-treated groups and in all endotoxin-treated groups with increased sex hormone concentrations, respectively. It could also be due to an effect on granulocytes per se, since the number of endotoxin-induced CD11b-positive cells in the glomeruli was increased only in the groups with increased sex hormone concentrations. Endotoxin-induced glomerular monocyte infiltration, however, was seen only in those groups in which developing ovarian follicles were lacking (i.e. day 14 pregnant, pseudopregnant and lactating rats), suggesting that developing ovarian follicles produce anti-inflammatory factors. These factors did not have an effect on endothelial or leukocyte adhesion molecule expression. We hypothesize that the presence of elevated progesterone concentrations increased the endotoxin-induced glomerular granulocyte infiltration, while endotoxin-induced glomerular monocyte infiltration was inhibited in the presence of developing ovarian follicles.

Acute-Phase Reaction↗

Cytokine production of in vitro stimulated peripheral lymphocytes during the course of pregnancy and pseudopregnancy in the rat.

PROBLEM: Does maternal lymphocyte cytokine production after in vitro stimulation vary with the stage of pregnancy in the rat? METHOD OF STUDY: Blood samples were taken during the estrus cycle in rats (n = 11). Thereafter, rats were rendered pregnant (n = 6) or pseudopregnant (n = 5) and blood samples were taken at days 4, 8, 11, 15, and 20 of pregnancy and pseudopregnancy. White blood cell (WBC) count was measured and whole blood was stimulated with phorbol 12-myristate 13-acetate and calcium ionophore; interferon-gamma (IFNgamma) and interleukin-4 (IL-4) production as well as (sub)populations of lymphocytes were measured using flow cytometry. RESULTS: We observed an increase of WBC in the second week of pregnancy and a slowly decreasing percentage of lymphocytes during the course of pregnancy. The percentage IFNgamma producing T-lymphocytes after in vitro stimulation was increased during pregnancy (for Th-lymphocytes only in the second week of pregnancy, for Tc-lymphocytes at all days). This increased IFNgamma production in pregnant T-lymphocytes was accompanied by an increase during pseudopregnancy, and therefore may result from increased sex hormone concentrations. The percentage IFNgamma producing natural killer (NK) cells after in vitro stimulation was decreased on day 20 of pregnancy. No effect of pregnancy or pseudopregnancy was seen on percentage IL-4 producing lymphocytes after in vitro stimulation. CONCLUSION: In the rat the IFNgamma production after in vitro stimulation varies during pregnancy and is increased, rather than decreased, during pregnancy.

Animals↗

Aromatase in the context of breast and endometrial cancer. A review.

Generally, estrogens are considered to be involved in the neoplastic transformation of endometrium. After the menopause these estrogens mainly originate from conversion of adrenal androgens by aromatization in body fat. However, in case of stromal hyperplasia of the ovaries, it cannot be excluded that production of aromatizable androgens by postmenopausal ovaries leads to increased availability of androgen precursors for intratumoral estrogen synthesis in the endometrial tissue as well. The local presence of androgens and the local expression and activity of aromatase is considered important for this steroidogenesis. In this review, we will discuss the available evidence that androgens, produced in hyperplastic ovarian stroma or body fat tissues, play a role in the development of endometrial cancer through conversion into estrogens, a reaction catalyzed in the endometrium by the enzyme aromatase cytochrome P450. As the presence of aromatase appeared to be a pathophysiological factor in the formation of breast cancer, the latter will be evaluated in relation to the development of endometrioid endometrial cancer as well, since both disorders appear partly estrogen dependent. As treatment with aromatase inhibitors appeared feasible in breast cancer, current knowledge of comparable treatment modalities in hormone dependent endometrial cancer will be reviewed.

Adipose Tissue↗

Women's opinion on the use and offer of ovarian reserve testing: a first step towards a wide ranged social discussion.

OBJECTIVE: To determine the opinion among three groups of women (sub-fertile women, fertile women and female medical students), concerning the use of ovarian reserve tests to determine the chance of an assisted reproductive techniques' (ART) induced pregnancy or a spontaneous pregnancy. DESIGN: Prospective study using questionnaires in three groups of women: patients visiting the out patient infertility clinic at the Academic Medical Centre Groningen, women who had delivered at least two children and female medical students. RESULTS: The response rate varied from 63% (female medical students) to 56% (fertile women with children) and 48% (sub-fertile women). The greater part of women of all three groups found it was up to the women themselves to decide whether or not to start fertility treatment, even though the ovarian reserve test indicated little chance of success. 71% of the sub-fertile women stated that any chance justified fertility treatment. None of the three groups of women were very enthusiastic about the use of these tests for family planning. CONCLUSIONS: Based on results of ovarian reserve tests women could decide not to partake of a - generally demanding - fertility treatment. The outcome of the study, however, does not support this: even low chances of success are found acceptable. The ability to determine the individual ovarian reserve makes this test also a suitable device for family planning. The discussion whether these new possibilities will be useful for reproductive science will greatly depend on women's attitude towards this issue.

Attitude to Health↗

Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: a pilot study.

BACKGROUND: The use of the natural cycle for IVF offers the advantage of a patient-friendly and low-risk protocol. Its effectiveness is limited, but may be improved by using a GnRH antagonist to prevent untimely LH surges. METHODS: In this pilot study, minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and simultaneous substitution with recombinant FSH was applied for a maximum of three cycles per patient. Main outcome measures were pregnancy rates per started cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 50 patients completed 119 cycles (2.4 per patient). Fifty-two embryo transfers resulted in 17 ongoing pregnancies [14.3% per started cycle; 32.7% per embryo transfer; 95% confidence interval (CI) 7.9-20.7% and 19.7-45.7%, respectively]. One dizygotic twin pregnancy occurred after transfer of two embryos, the other pregnancies were singletons. The cumulative ongoing pregnancy rate after three cycles was 34% (95% CI 20.6-47.4%). Live birth rate was 32% per patient (95% CI 18.8-45.2%). CONCLUSIONS: Pregnancy rates after IVF with minimal, late follicular phase stimulation are encouraging. Considering the low-risk and patient-friendly nature of this protocol, it may be a feasible alternative to IVF with ovarian hyperstimulation.

Adult↗

[Preimplantation genetic screening for numerical chromosomal abnormalities in embryos from women of 35 years of age and older; first results in The Netherlands].

OBJECTIVE: To assess the results of preimplantation genetic screening (PGS) for numerical chromosomal abnormalities in embryos from women of 35 years of age and older. DESIGN: Prospective, descriptive. METHOD: Women who were at least 35 years received standard IVF/ICSI treatment including ovarian hyperstimulation, after which matured oocytes were recovered and inseminated. Three days after insemination, one cell was biopsied from each of the available embryos. In these cells, the copy number of 5 (first 21 patients) or 8 chromosomes was determined using fluorescence in situ hybridisation (FISH). Only embryos with a normal or unknown FISH result were implanted in the uterus. Data were collected in an electronic database. RESULTS: PGS was done for 28 IVF- and 22 ICSI-treatments; the average age of the 50 women at the beginning of treatment was 38.5 years. There were 360 embryos generated; of the 288 biopsied embryos 156 (54%) contained an abnormal number of chromosomes. In 45 women, 1 or 2 embryos were transferred. This resulted in 8 ongoing pregnancies (8/50; 16%) and the birth of 9 children, all of whom were found to be healthy on a paediatric examination at 3 to 10 months of age. In 4 cases there was no embryo transfer because all the embryos were chromosomally abnormal. CONCLUSION: In the first 50 patients in The Netherlands, PGS resulted in an ongoing pregnancy rate of 16% per woman. All children showed normal growth and development.

Adult↗

An in vitro model for purging of tumour cells from ovarian tissue.

BACKGROUND: Cryopreservation and autografting of ovarian tissue may preserve fertility after cancer treatment, but could be hampered by tumour cell contamination. Epithelial tumour cell lysis can be obtained with cytotoxic T cell retargeting through the bispecific antibody BIS-1, with combined affinity for the T-cell receptor and epithelial glycoprotein-2 (EGP-2). Our aim was to study the concept of tumour cell purging in the setting of a suspension of ovarian tissue. METHODS: Human ovarian tissue was brought into suspension by mechanical and enzymatic treatment. Cells of the MCF-7 breast cancer cell line and activated human lymphocytes were co- incubated for 4 h with or without BIS-1 and with or without ovarian suspension. After incubation, MCF-7 cell death and cell growth were evaluated by fluorescent cell detection and MTT assay, respectively. Ovarian tissue morphology was evaluated immunohistochemically. RESULTS: MCF-7 cell death and cell growth inhibition increased with increasing ratios of lymphocytes to MCF-7 cells. BIS-1 addition gave further augmentation, with a maximum depletion of growing MCF-7 cells of 89% (SD 11%) versus without BIS-1, 23% (SD 15%; P < 0.001). Follicles remained morphologically intact. CONCLUSIONS: Purging of added epithelial tumour cells from ovarian tissue with BIS-1 is possible in vitro. Morphologically, follicles remain intact after this procedure. This method may contribute to safer replacement of ovarian tissue in female cancer survivors.

Adolescent↗

Intrauterine insemination versus fallopian tube sperm perfusion for non tubal infertility.

BACKGROUND: Controlled ovarian hyperstimulation (COH) together with intrauterine insemination (IUI) is commonly offered to couples with infertility factors not involving the fallopian tubes. Intrauterine insemination gained its popularity because it is simple, non-invasive and cost-effective technique. Another simple non invasive method was introduced called fallopian tube sperm perfusion (FSP). This technique was developed to ensure the presence of higher sperm densities in the fallopian tubes at the time of ovulation than standard IUI provides. Fallopian tube sperm perfusion is based on pressure injection of 4 ml of sperm suspension with attempt of sealing of the cervix to prevent semen reflux. The IUI technique on the other hand is based on intrauterine injection of 0.5 ml of sperm suspension without flushing the tubes. A number of randomised controlled trials have been published comparing the efficacy of FSP with standard IUI. There were considerable variations in the results. The aim of this review was to determine whether outcomes differ between FSP and IUI in improving the probability of conception. OBJECTIVES: To investigate whether outcomes differ between fallopian tube sperm perfusion and intrauterine insemination in the treatment of non tubal subfertility resulting in pregnancies and live births. SEARCH STRATEGY: We searched the Menstrual Disorders & Subfertility Group trials register (24 March 2003), MEDLINE (January 1966 to July 2003) and EMBASE (January 1988 to July 2003). Abstracts of the American Society for Reproductive Medicine (1987 to 2003) and European Society for Human Reproduction and Embryology (1987 to 2003) meetings were searched with the same key- or text words. SELECTION CRITERIA: Only randomised controlled studies comparing fallopian tube sperm perfusion with intrauterine insemination were included in this review. The method of allocation was assessed to determine whether each study was truly randomised or pseudo-randomised. Only first period data of cross-over trials were included for analysis. Couples who have been trying to conceive for at least one year were included but only when the female partner had patent tubes. DATA COLLECTION AND ANALYSIS: Two independent reviewers (AC and MJ) selected the trials for inclusion based on the quality of the studies. MAIN RESULTS: Overall six studies involving 474 couples were included in the meta-analysis. Only one study assessed live birth rates (OR 1.17, 95% CI 0.39 3.53). The results for pregnancy rate per couple were statistically significant with FSP showing higher pregnancy rates (OR 1.85, 95% CI 1.23 to 2.79 using the odds ratio with the fixed effect model. To check the results the random effect model was used, which gave a wider confidence interval which crossed the line of no significance (OR 1.76, 95% CI 0.77 to 4.05). As a result, these outcomes should be interpreted with caution. Subgroup analysis revealed that couples suffering from unexplained subfertility benefit from FSP over IUI, resulting in significantly higher pregnancy rates (OR 2.88, 95% CI 1.73 to 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 to 3.80). REVIEWERS' CONCLUSIONS: FSP may be more effective for non-tubal subfertility, but the significant heterogeneity should be taken into account. As a result no advice based on the meta-analysis could be given for the treatment of non-tubal subfertility. Subgroup analysis, which did not show evidence of statistical heterogeneity, suggested that couples with unexplained infertility may benefit from FSP over IUI in terms of higher pregnancy rates. FSP may therefore be advised in couples with unexplained subfertility. Results suggested the possibility of differential effectiveness of FSP depending on catheter choice.

Fallopian Tubes↗

Semen preparation techniques for intrauterine insemination.

BACKGROUND: Semen preparation techniques for assisted reproduction, including intrauterine insemination (IUI), were developed to separate the motile morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg. The yield of as many motile, morphologically normal spermatozoa might influence treatment choices and therefore outcomes. OBJECTIVES: To compare the effectiveness of gradient, swim-up, or wash and centrifugation in subfertile couples undergoing intrauterine insemination (IUI) on clinical outcome as well as on semen parameters. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group's trials register (30 June 2003), MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), Science Direct Database (1966 to July 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), National Research Register (2000 to Issue 2, 2003), Biological Abstracts (2000 to June 2003), CINAHL (1982 to July 2003) and reference lists of relevant articles. We also contacted experts and authors in the field. SELECTION CRITERIA: Parallel randomised controlled trials (RCTs), comparing the efficacy of semen preparation techniques used for subfertile couples undergoing IUI, were included. RCTs or split sample studies examining semen parameters after different semen preparation techniques were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Two randomised controlled trials comparing clinical outcomes, including 81 participants in total, were included in the meta-analysis (Dodson 1998-I/ II; Xu 2000-I/ II). Both studies compared swim-up technique versus gradient technique in 65 subfertile couples undergoing IUI. One study compared the effectiveness of both techniques with wash technique. No trials reported the primary outcome of live birth. There was no statistically significant difference between pregnancy rates (PR) for swim-up versus gradient / wash centrifuge (Peto OR 0.55, 95% CI 0.17 to 1.76; Peto OR 1.74, 95% CI 0.2 to 14.9; PR/ couple swim-up 20%, gradient 40%, wash 12.5%) or gradient versus wash centrifuge (Peto OR 4.01, 95% CI 0.82 to 19.56; PR/ couple swim-up 15%, gradient 20%). There was no significant difference in the miscarriage rate (MR) per couple between either of the three treatment groups in the one trial reporting this outcome (MR/ couple swim-up 0%, gradient 10.3%, wash 0%. MR/ pregnancy gradient 30.3%). There was no statistically significant difference in the multiple pregnancy rate (MPR) per couple between either of the three treatment groups in Dodson 1998-I/ II (MPR/ couple swim -up 0%, gradient 0%, wash 6.3%). One triplet pregnancy was recorded. Fifteen studies comparing semen parameters after processing were included. Two studies were included in the meta-analysis, we were not able to pool results. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend any specific preparation technique. Large high quality randomised controlled trials, comparing the effectiveness of a gradient and/ or a swim-up and/ or wash and centrifugation technique on clinical outcome are lacking. Further randomised trials are warranted. Results from studies comparing semen parameters may suggest a preference for gradient technique, but firm conclusions cannot be drawn and the limitations should be taken into consideration.

Centrifugation, Density Gradient↗

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↗

Single versus double intrauterine insemination (IUI) in stimulated cycles for subfertile couples.

BACKGROUND: Intra uterine insemination (IUI), with or without controlled ovarian hyperstimulation (COH), is one of the treatment modalities offered to couples who have tried to conceive for at least one year (subfertile couples). It has been suggested that increasing the number of inseminations from one per cycle to two might increase the probability of conception. OBJECTIVES: To determine if there is a difference in live birth or pregnancy rates for subfertile couples using single or double intrauterine insemination in stimulated cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility group trials register (searched 8 July 2002), the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2002), MEDLINE (January 1966 to July 2002), EMBASE (January 1988 to July 2002), SCIENCE Direct Database (January 1966 to July 2002), Confsci (January 1973 to 15 July 2002), Pascal (January 1984 to July 2002) and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised controlled, parallel trials of single versus double intrauterine inseminations in simulated cycles in subfertile couples. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Three studies involving 386 women were included. There was no data for the main outcome measure of live birth per couple or ongoing pregnancy rates, and none presented comparative data for adverse events. The results of two studies that reported pregnancy rate per couple did not show a significant effect of using double insemination (Peto OR 1.45, 95% CI 0.78-2.70). REVIEWER'S CONCLUSIONS: Based on the results of pregnancy rate per couple of two trials, double intrauterine insemination showed no significant benefit over single intrauterine insemination in the treatment of subfertile couples with husband semen. There are no meaningful data to offer advice regarding clinical practice on the basis of this review.

Female↗

Total white blood cell counts and LPS-induced TNF alpha production by monocytes of pregnant, pseudopregnant and cyclic rats.

Pregnancy in the rat may be associated with an activated innate immune system. Therefore, we investigated monocyte function as well as total white blood cell (WBC) counts during the follicular phase of the ovarian cycle, pregnancy and pseudopregnancy in the rat. Rats were equipped with a permanent jugular vein cannula, and 0.43 ml blood samples were taken from this cannula during the 4 days of the regular oestrus cycle of the rat (n=12). Thereafter, six rats were rendered pregnant, and the other six rats were rendered pseudopregnant according to standard methods. Blood samples were withdrawn from the cannula on days 4, 7 and 11 of pseudopregnancy and on days 4, 7, 11 and 20 of pregnancy. From each blood sample, 0.4 ml was stimulated with lipopolysaccharide (LPS) and monocyte intracellular cytokine production measured using flow cytometry. 30 microl of the blood was used to measure WBC counts and differential WBC counts. The results showed that the number of WBC was significantly increased only on day 11 of pregnancy compared with the follicular phase, and that this was due to the increased numbers of polymorphonuclear (PMN) cells. The percentage of TNF alpha-producing monocytes was increased on all days of pseudopregnancy and on day 11 of pregnancy. The fact that the percentage of monocytes producing TNF alpha upon an LPS stimulus was increased during the post-implantation phase of pregnancy and during pseudopregnancy as compared to the follicular phase may indicate that these conditions are proinflammatory conditions. For the post-implantation phase of pregnancy, this is once more stressed by the increased numbers of WBC and PMN.

Animals↗