Background Guidelines recommend diagnostic laparoscopy in subfertile women with known co-morbidities in their medical history. Aggregated evidence underpinning these recommendations is, however, currently lacking.Objective The objective of this study was to perform a systematic review and meta-analysis of the available evidence on the association between items reported during medical history taking and tuboperitoneal pathology. Selection criteria All relevant studies that compared medical history with the presence or absence of tubal pathology.Data collection and analysis Studies comparing medical history with the presence or absence of tubal pathology were included. A diagnosis of tubal pathology had to be made by hysterosalpingography, laparoscopy or a combination of both. In the absence of invasive tubal testing, tuboperitoneal pathology was considered to be absent in case of intrauterine pregnancy. Homogeneity between studies was assessed, and the association between medical history and tubal pathology was expressed as a common odds ratio with a 95% CI. No language restriction was applied. Main resultsWe included 32 studies. In cohort studies, strong associations were found for a history of complicated appendicitis (OR 7.2, 95% CI 2.2-22.8), pelvic surgery (OR 3.6, 95% CI 1.4-9.0) and pelvic inflammatory disease (PID) (OR 3.2, 95% CI 1.6-6.6), and in case-control studies, for a history of complicated appendicitis (OR 3.3, 95% CI 1.8-6.3), PID (OR 5.5, 95% CI 2.7-11.0), ectopic pregnancy (OR 16.0,, endometriosis (OR 5.9, 95% CI 3.2-10.8) and sexually transmitted disease (OR 11.9,3).Author's conclusions Subfertile women reporting a history of PID, complicated appendicitis, pelvic surgery, ectopic pregnancy and endometriosis are at increased risk of having tuboperitoneal pathology. In these women, diagnostic laparoscopy should be offered early in the fertility work-up.

Estrogen-dominant follicular fluid (FFe) and granulosa-luteal cell conditioned media, in contrast to androgen-dominant FF (FFa), contain barely detectable levels of insulin-like growth factor binding protein-4 (IGFBP-4) by ligand binding techniques. The current study was designed to evaluate the possibility of an IGFBP-4 protease in FFe, which may alter the affinity of IGFBP-4 for insulin-like growth factors (IGFs), rendering IGFBP-4 undetectable by ligand binding techniques. FFe and FFa were obtained from regularly menstruating women, and FFe was also obtained during in vitro fertilization procedures. Mixing experiments were performed by using human recombinant IGFBP-4 or IGFBP-4 in nonpregnancy serum (NPS) as substrate and FF as the source of the putative protease. Incubation of NPS at 37C for 5 h in the presence of FFe resulted in the reduction of IGFBP-4 to barely detectable levels when analyzed by Western ligand blotting, with no change occurring in the levels of the other binding proteins present in NPS. In contrast, incubation of FFa with NPS under similar conditions had no effect on the levels of IGFBP-4. The disappearance of IGFBP-4 when NPS was mixed with FFe exhibited optimal pH-dependence at pH 7-9. Inhibition of the putative protease by aprotinin, ethylenediaminetetraacetic acid, and 1,10-phenanthroline supports its identification as a metalloserine protease. Western immunoblot analysis detected the presence of a proteolytic fragment of approximately 17-18 kDa after incubation of recombinant IGFBP-4 in the presence of FFe but not in the presence of FFa. Similar incubation of other recombinant human IGFBPs did not reveal their degradation, further suggesting that the protease in FFe is specific for IGFBP-4. These data demonstrate the presence of an IGFBP-4-specific metalloserine protease in FFe but not in FFa, and they suggest that proteolytic cleavage may be responsible for effectively decreasing levels of inhibitory IGFBP-4 and thus increasing bioavailability of IGF peptides within estrogen-dominant follicles. The importance of this mechanism may lie in providing the dominant follicle with more available IGFs to synergize with gonadotropins in stimulating estradiol production and in inhibiting this synergy in androgen-dominant and atretic follicles.

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