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Biomedical subjects

R J van Kooij

Publications and source records attributed to R J van Kooij.

At least 19 recordsLinked to original sources

Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study.

In this randomized crossover trial we investigated whether the use of controlled ovarian hyperstimulation with low-dose human menopausal gonadotrophin in couples with male subfertility leads to a higher probability of conception when intrauterine insemination (IUI) is applied. We also investigated whether the efficacy of IUI in natural or stimulated cycles was related to the severity of male subfertility. Seventy-four couples completed 308 treatment cycles. Thirteen pregnancies occurred after IUI in a natural cycle (pregnancy rate per completed cycle: 8.4%) and 21 after IUI in a stimulated cycle (pregnancy rate per completed cycle: 13.7%). The difference between the two treatment modalities was not statistically significant. The efficacy of IUI in stimulated cycles was related to the severity of the semen defect. In couples with a total motile sperm count < 10 x 10(6), ovarian stimulation did not improve treatment outcome, while it did in couples with a total motile sperm count > or = 10 x 10(6). Compared with the expected chance of conceiving spontaneously without treatment, both natural and stimulated cycles improved the probability of conception. We conclude that, for the group as a whole, ovarian stimulation did not improve the probability of conception. However, in couples with less severe semen defects, ovarian stimulation did improve the probability of conception.

Adult

Protein C inhibitor may modulate human sperm-oocyte interactions.

Protein C inhibitor (PCI) is a heparin-binding plasma serine protease inhibitor that was originally identified as an inhibitor of activated protein C. PCI has a broad protease specificity, inhibiting several proteases in hemostasis and fibrinolysis by acting as a suicide substrate. Recently it has been reported that proteases of the reproductive system, such as acrosin, prostate-specific antigen, and tissue kallikrein, can also be effectively inhibited by PCI. However, a direct relation between PCI and physiological events during fertilization has not yet been established. An attempt was made to monitor and localize the inhibition of the sperm protease acrosin by PCI. Localization experiments for PCI on epididymal spermatozoa showed that PCI is present on the acrosomal cap of human spermatozoa, which demonstrates the early presence of PCI in the male reproductive tract. Induction of the acrosome reaction in ejaculated human spermatozoa resulted in the disappearance of PCI from the plasma membrane overlying the acrosomal head and the appearance of a strict distribution at the equatorial segment of human spermatozoa. The activity of acrosin in sperm extracts could be effectively inhibited by PCI. Zona-binding assays showed that active PCI is able to block sperm-egg binding in a concentration-dependent manner. The combination of the potent inhibition of acrosin and sperm-egg binding by PCI and the localization studies suggested that PCI may protect spermatozoa against premature acrosome reaction and degradation, thereby modulating the acrosin activity so that it can coincide with binding to the oocyte.

Acrosin

[Male subfertility, modern reproduction techniques and transmission of genetic abnormalities].

Somatic cells of males with azoospermia or oligozoospermia (sperm density < 20 million sperm cells/ml) were found to contain increased percentages of chromosomal abnormalities. Subfertile males with a normal somatic karyogram were found to have increased rates of aneuploidy in sperm. This creates risks for the offspring after fertilization with intracytoplasmatic sperm injection (ICSI). Certain gene mutations on the Y chromosome cause severe oligo- or azoospermia and will, in case of successful reproduction with ICSI, be transmitted to male offspring in 100% of the cases. The same holds true, irrespective of sex, of mutations responsible for cystic fibrosis. In non-random groups of ICSI pregnancies, higher proportions of de novo sex-chromosomal abnormalities have been found than expected. In addition, there are increased proportions of paternally inherited structural autosomal anomalies. Extrapolation of the findings is not yet possible, however.

Chromosome Aberrations

Intracytoplasmic sperm injection (ICSI) and chromosomally abnormal spermatozoa.

An infertile couple was referred for intracytoplasmic sperm injection (ICSI) because of primary infertility and oligoasthenoteratozoospermia (OAT) in the male. It was observed that although the sperm cells presented with an unusual head size and multiple tails they were able to fertilize the oocytes after ICSI. Subsequent molecular cytogenetic analysis demonstrated de-novo chromosome abnormalities in virtually all sperm cells with 40% diploidy and 24% triploidy in addition to aneuploidy for the sex chromosomes.

Adult

Age-dependent decrease in embryo implantation rate after in vitro fertilization.

OBJECTIVE: To investigate the relation between the implantation rate per embryo after replacement in IVF-ET in relation to female age. DESIGN: Retrospective study using linear and biphasic models in a multivariate analysis. SETTING: Academic tertiary care institution. INTERVENTION(S): In vitro fertilization-ET and determination of gestational sacs at 6 to 7 weeks of pregnancy buy ultrasound. MAIN OUTCOME MEASURE(S): Implantation rate as defined by the number of gestational sacs per embryo replaced. RESULT(S): Woman's age and embryo morphology were strongly related to the implantation rate, indication for IVF-ET and cycle rank number also were related significantly but less strongly. A linear model was built describing the decrease in implantation rate with age, resulting in a decrease of approximately 7%. A biphasic model was tested also and performed significantly better, resulting in a yearly decrease of > 20% after 37 years of age. CONCLUSION(S): The most important independent factors related to the ability of embryos to implant are female age and embryo morphology. The best way to describe the relation with female age is biphasic model with a discontinuity at approximately 37 years of age.

Aging

Is there a carryover effect of mild ovarian hyperstimulation with gonadotropins on the subsequent cycle?

OBJECTIVE: To investigate the effect of mild ovarian hyperstimulation on hormonal and sonographic variables of the subsequent natural cycle. DESIGN: Prospective study of three consecutive cycles. SETTING: University Hospital, Department of Reproductive Medicine, Division of Obstetrics and Gynecology. PATIENTS: Twelve couples with subnormal semen as the only identifiable cause of subfertility. INTERVENTIONS: Subjects were offered IUI for three cycles. In the second cycle, mild ovarian hyperstimulation with 75 IU IM hMG was applied daily and ovulation was induced with 5,000 IU hCG. In the first and third both natural cycles, serum samples were obtained for hormone measurements and ultrasound (US) scanning of the ovaries was performed. MAIN OUTCOME MEASURE: To determine whether there was a carryover effect of mild ovarian hyperstimulation as applied in the second cycle, hormone levels and US scans of cycle 3 were compared with those of cycle 1. RESULTS: None of the variables of cycle 3 were significantly different from those of cycle 1. CONCLUSION: Because hormonal and sonographic variables in the subsequent natural cycle remain unchanged, a carryover effect of mild ovarian hyperstimulation with gonadotropins seems unlikely.

Adult

Is there still a place for intra-uterine insemination as a treatment for male subfertility? A review.

Using the results of randomized and controlled studies, it was assessed whether there is still a place for intra-uterine insemination (IUI), with or without controlled ovarian hyperstimulation (COH), as a treatment for male subfertility. It is concluded that, in the case of a moderate to severe semen defect, well-timed IUI should be applied in natural cycles only, because COH does not further improve treatment outcome. In contrast, in the case of a mild semen defect, the present evidence indicates that COH improves the probability of conception. If COH is applied, stimulation should be mild in order to prevent multiple pregnancies and the ovarian hyperstimulation syndrome.

Clinical Trials as Topic

Intra-uterine insemination or timed intercourse after ovarian stimulation for male subfertility? A controlled study.

In this randomized trial we investigated whether intra-uterine insemination (IUI) in couples with male subfertility leads to a higher probability of conception than timed intercourse after ovarian stimulation with human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). A total of 76 couples started 249 cycles, of which 47 were cancelled to prevent multiple pregnancies or hyperstimulation. After 202 completed treatment cycles, 15 pregnancies occurred, 11 after IUI and four after timed intercourse. The pregnancy rate per completed cycle with IUI was 10.3% (95% confidence interval: 5.5-17.5%) and 4.2% (1.2-10.1%) with timed intercourse. Compared with the estimated spontaneous chance to conceive, IUI after ovarian stimulation appeared to be more effective in the first three cycles. We conclude that in subfertile couples with a male factor, IUI tends to improve the probability of conception as compared to timed intercourse when ovarian stimulation is applied, and we advise such treatment for three cycles.

Adult

The pattern of the luteinizing hormone surge in spontaneous cycles is related to the probability of conception.

OBJECTIVE: To determine whether the pattern of the LH surge in a treatment cycle with artificial insemination with the husband's semen (AIH) because of cervical factor infertility is associated with the probability of conception. DESIGN: Retrospective study. SETTING: University Hospital, Department of Obstetrics and Gynecology. PATIENTS: Couples with cervical factor infertility as the main cause of subfertility. INTERVENTIONS: Luteinizing hormone monitored AIH. MAIN OUTCOME MEASURE: Whether or not a pregnancy occurred after AIH. RESULTS: There were 53 pregnancies in 382 IUI cycles (pregnancy rate [PR] per cycle: 13.9%). The PR was significantly higher in cycles with an LH surge of 2 days compared with cycles with a surge of 1 day. The probability of conception also seemed to be related to the height of the LH surge. CONCLUSION: The pattern of the LH surge in patients with cervical factor infertility is related to the outcome of a treatment with AIH.

Adult

Determination of sex ratio of spermatozoa with a deoxyribonucleic acid-probe and quinacrine staining: a comparison.

OBJECTIVE: To evaluate sex selection of spermatozoa. DESIGN: A deoxyribonucleic acid (DNA) probe (pDP34) detecting distinguishable loci on both X and Y chromosome was used to validate the quinacrine-staining method that is often used for determination of the percentage of Y-bearing sperm. Sperm samples were centrifuged over Percoll to obtain samples with a high X:Y ratio according to the quinacrine-staining method. Controls (sperms before processing over Percoll) and processed sperms were subjected to DNA extraction and analysis with the DNA probe. RESULTS: The DNA analysis revealed a 1.0 X:Y ratio of the spermatozoa before and after Percoll separation. CONCLUSION: We conclude that the quinacrine method is not suitable for evaluation of methods that claim to separate X and Y-bearing sperm.

Blotting, Southern

Influence of polymorphonuclear granulocytes on the zona-free hamster oocyte assay.

To gain more insight into a possible detrimental influence of polymorphonuclear granulocytes (PMN) on fertility, PMN were added to spermatozoa and oocytes in the hamster oocyte assay. Addition of 2.5 x 10(6)/ml PMN to the sperm suspension at the start of the first incubation period (capacitation period) resulted in a significant decrease (P less than 0.03) in the number of decondensed sperm-heads per hamster oocyte (the decondensation index). When a concentration of 0.5 x 10(6)/ml PMN was used, no decrease was found. Stimulation of PMN by phorbol myristate acetate (PMA) did not enhance the inhibitory action of PMN. After incubation of oocytes with PMN for 1 h, an almost total inhibition of decondensation was observed. A significant inhibition could also be obtained when unstimulated PMN (2.5 x 10(6] were added at the start often 3 h coincubation period of spermatozoa and oocytes (P less than 0.004). The inhibition by PMN decreased to a nonsignificant level when the hydroxyl radical scavenger thiourea was present. The possible mechanisms by which PMN affect the results of the hamster oocyte assay and the possible implications of the presence of PMN in the genital tract are discussed.

Adult

The presence of zonae pellucidae influences fusion rates between spermatozoa and zona free hamster oocytes.

Human zonae pellucidae were added to suspensions of capacitating spermatozoa. The zonae were prepared from oocytes that remained unfertilized in our in-vitro fertilization (IVF) programme. After capacitation, zona free hamster oocytes were added and the penetration rate of the hamster oocytes was determined. Controls without the addition of zonae were run in parallel. A distinct enhancement of the penetration rate was found when zonae were present during capacitation, using sperm of fertile donors. Sperm of several infertile men did not respond to the presence of zonae with higher penetration rates. It was concluded that the zona pellucida is involved in the induction of the acrosome-reaction of human spermatozoa. In addition the incubation system with zonae as described might be useful for the identification of infertile semen.

Animals