[Recurrent miscarriage turns out to be lung cancer]. / Herhaalde miskraam blijkt longkanker.

BACKGROUND: If a positive pregnancy test is followed by profuse vaginal bleeding, the diagnosis of miscarriage can generally be made. Sometimes, however, elevated hCG levels may be associated with a phantom pregnancy, which may be a paraneoplastic symptom. CASE DESCRIPTION: A 27-year-old woman was referred for a diagnosis after having experienced 3 consecutive miscarriages. The diagnostic workup could not identify an underlying cause. After 3 more biochemical miscarriages, the original diagnosis was called into question and extensive testing for ectopic hCG production was performed. It appeared that the false pregnancies were paraneoplastic symptoms of an hCG-producing non-small cell lung cancer. After a lobectomy, the hCG levels returned to normal and a spontaneous pregnancy and uncomplicated delivery followed. CONCLUSION: Phantom pregnancy as a paraneoplastic symptom is extremely rare, but should be considered in patients presenting with recurrent, non-objectifiable miscarriages. Careful documentation of the menstrual cycle is necessary for early detection of the condition. The fact is that vaginal bleeding after a positive pregnancy test can still be a normal menstruation.

Review of the role of the plasminogen activator system and vascular endothelial growth factor in subfertility.

OBJECTIVE: To assess the importance of the plasminogen activator (PA) system and vascular endothelial growth factor (VEGF) in subfertility. DESIGN: Review. SETTING: Two university IVF centers. INTERVENTION(S): Systematic literature search (MEDLINE, Science Direct, and bibliographies of published works). RESULT(S): The PA system in the male is involved in the passage of spermatozoa precursor cells over the blood-testis barrier, the epididymal maturation of spermatozoa, the modifications of the sperm surface for capacitation, the acrosome reaction and zona pellucida attachment, and finally the facilitation of spermatozoa to move into the fallopian tubes. In the female, the PA system plays a role during ovulation in the release of the oocyte from the follicle, the facilitation of oocyte movement into the fallopian tubes, and the extracellular matrix degradation important for angiogenesis in the ovary. The function of VEGF during fertilization is largely unknown. It has been suggested that VEGF is important for the fluid and proteins in semen and fluid secretion in the female genital tract, thereby influencing sperm motility and survival. The latter could be due to an effect of VEGF on testicular microvasculature, through which an adequate microenvironment for spermatogenesis is provided. In the female, VEGF is involved in the regulation of the cyclic ovarian angiogenesis, the development and/or selection of follicles, the accumulation of follicular fluid, and corpus luteum angiogenesis. CONCLUSION(S): The role of the PA system and VEGF in reproduction most likely is of great interest. However, much of the data are derived from experimental animal studies. So far, information on the importance of these systems in humans is scarcely investigated. Therefore, further research is required to elucidate the role of the PA system and VEGF in the pathogenesis and prevention of male and female subfertility. Eventually, this will contribute to the improvement of the diagnosis of subfertility and may possibly lead to targeted therapeutic management of subfertility.

Possible role of the plasminogen activation system in human subfertility.

OBJECTIVE: To correlate components of the plasminogen activator (PA) system with fertility outcome parameters in participants in an IVF/intracytoplasmic sperm injection (ICSI) procedure. DESIGN: Case-control study. SETTING: Outpatient clinic for IVF/ICSI treatment at the Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. PATIENT(S): One hundred and fifty-six couples undergoing an IVF/ICSI procedure. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex concentrations in the ejaculate, spermatozoa, and follicular fluid (FF). RESULT(S): Concentrations of t-PA were higher in spermatozoa of the male factor subfertility group (geometrical mean, 77.1 pg/million spermatozoa; 25th-75th percentiles, 31.8-211.2), compared to fertile men (geometrical mean, 1.91; 25th-75th percentiles, 0.74-5.79) and idiopathic subfertile men (geometrical mean, 3.14; 25th-75th percentiles, 0.97-9.97). Furthermore, the concentration of t-PA in spermatozoa was significantly associated with pregnancy (odds ratio [OR], 0.995). Likewise, a trend was shown for higher t-PA concentrations in the FF of women with fallopian-tube pathology (geometrical mean, 18.5 pg t-PA/mg protein; 25th-75th percentiles, 11.4-25.7) or endometriosis (geometrical mean, 18.8; 25th-75th percentiles, 11.4-27.1), compared to fertile women (geometrical mean, 14.3; 25th-75th percentiles, 10.3-17.6) and idiopathic subfertile women (geometrical mean, 13.9; 25th-75th percentiles, 9.5-17.8). Also, t-PA in FF is associated with the proportion of cleaved embryos (regression coefficient, 0.16). The concentrations of u-PA, PAI-1, and t-PA-PAI-1 complex were comparable between diagnostic subgroups in both men and women. CONCLUSION(S): The t-PA concentrations in spermatozoa and FF tend to be higher in human subfertility, and seem to be associated with some fertility outcome parameters.

C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration.

OBJECTIVE: To determine the frequency of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism in fertile and subfertile males, and the MTHFR-dependent response of sperm concentration after folic acid and/or zinc sulfate intervention. DESIGN: Double-blind, placebo-controlled intervention study. Two outpatient fertility clinics and nine midwifery practices in The Netherlands. PATIENT(S): One hundred thirteen fertile and 77 subfertile males. Daily capsules of folic acid (5 mg) and/or zinc sulfate (66 mg), or placebo for 26 weeks. MAIN OUTCOME MEASURE(S): Prevalence of C677T MTHFR polymorphism and the response of sperm concentration related to MTHFR carriership after intervention treatment. RESULT(S): The C677T methylenetetrahydrofolate reductase genotypes were comparable in fertile and subfertile males. Independent of fertility state, sperm concentration significantly increased in wild-types after folic acid and zinc sulfate treatment only. Heterozygotes and homozygotes did not significantly benefit from either treatment. CONCLUSION(S): C677T methylenetetrahydrofolate reductase polymorphism is not a risk factor for male factor subfertility. In contrast to heterozygotes and homozygotes for C677T MTHFR polymorphism, sperm concentration in wild-types significantly improved after folic acid and zinc sulfate intervention. A stronger role of other folate genes on spermatogenesis is suggested.