1 Center for Family Planning, Gynaecological Endocrinology & Reproductive Medicine Grevenbroich, 2 Biometric Research Group, Clinic for Thoracic and Cardiovascular Surgery, Heinrich-Heine University of Duesseldorf, 3 Department of Gynaecological Endocrinology, University of Heidelberg and 4 Department of Reproductive Medicine, Staedtische Kliniken Duesseldorf gGmbH, Frauenklinik Benrath, Germany
5 To whom correspondence should be addressed at: Rheydter Strasse 143, 41515 Grevenbroich, Germany. gnoth{at}uni-duesseldorf.de
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Abstract |
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Key words: definition of subfertility/fertility awareness/management of infertility/prevalence of infertility/time to pregnancy
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Introduction |
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Time to pregnancy |
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Wang et al. (2003) prospectively observed 518 newly married Chinese textile workers (2034 years of age) trying to conceive. They recorded vaginal bleeding, sexual intercourse and collected daily first-morning urine specimens for up to 1 year or until a clinical pregnancy was achieved. Survival curves (Kaplan and Meier, 1958
) were calculated for proportion of conceptions over number of menstrual cycles. In their cohort of women,
50% became clinically pregnant in the first two cycles and >90% in the first six cycles. They found that the monthly fecundity varied between 30 and 35%.
In this journal we reported on 346 women using natural family planning methods to conceive (Gnoth et al., 2003). They were observed from their first cycle of trying to conceive onwards. Only cycles with intercourse in the fertile phase were included. Pregnancy was assessed by either ultrasound, positive pregnancy test or a luteal phase >18 days. In both latter cases, only later-confirmed clinical pregnancies (live birth, ectopic implantation or clinical abortion) were included in the analyses. KaplanMeier survival analyses (cumulative probabilities of conception, CPC) were carried out for the whole group and separately for those who finally conceived (truly fertile couples). A total of 310 pregnancies occurred among 346 women in a maximum of 29 cycles of observation with a mean of 3.56 and SD of 4.03 for a total of 1208 cycles observed. Only the data of 340 out of 346 women could be included in the analysis because for six women out of those who finally conceived TTP was inaccurate because some cycles were completely missed. Estimated CPC for the total group (340 women included) at one, three, six and 12 cycle(s) were 38, 68, 81 and 92% respectively. For those who finally conceived (truly fertile couples, 304 women included), the respective pregnancy rates were 42, 75, 88 and 98%. Most couples conceived within six cycles of timed intercourse. Thereafter we have to assume slight or serious subfertility in every second couple. As expected, CPC declined with age because heterogeneity in fecundity increases. In the subgroup of truly fertile couples, CPC was statistically age independent (as judged by the Wilcoxon test) because of high homogeneity even with advancing age.
Both studies underline the positive effect of timed intercourse on pregnancy probabilities for women, using their fertility potential optimally. This was recently also emphasized by Stanford et al. (2002). Vulvar mucus observations seem to be an effective tool in self-assessment of peak fertility in the menstrual cycles and seem to be superior to the relative timing of intercourse to ovulation (Bigelow et al., 2004
). A current prospective study comparing clinical pregnancy rates in intrauterine insemination cycles with either cycle monitoring by ultrasound and LH or exclusively vulvar mucus observation should further evaluate its effectiveness.
In this journal a very important prospective study was published on the long-term follow-up of subfertile couples with a history of >1 year of unprotected intercourse and no treatment thereafter (Snick et al., 1997). They found that couples with a history of 1 year unwanted non-conception still have a cumulative live birth rate of 52.5% at 36 months. The cumulative live birth rate was highest in couples with unexplained infertility and low for severe male, tubal and ovulation defects. Prognostic factors related to higher cumulative pregnancy rates were duration of infertility <24 months, a previous pregnancy in the same partnership and a female age <30 years (multiplication factors of 1.41.5). Gleicher et al. (1996)
reported a cumulative pregnancy rate of 19.9% after 12 months in a subfertile population with unwanted non-conception of
1 year's duration with a total of 9079 inactive treatment months of observation. In an important multicentre study Collins et al. (1995)
observed among 2198 couples with unwanted non-conception of >1 year (18 364 untreated months of observations on 873 untreated couples, combined with observations before the first treatment among 1325 later treated couples with 9761 untreated months before the first treament) a cumulative rate of conceptions leading to live birth of 14.3% at 12 months. Interestingly,
20 years ago Hull et al. (1985)
published similar results.
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Discussion |
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The decision to treat depends on the spontaneous pregnancy prospect and whether the treatment has proven effectiveness (Collins and Van Steirteghem, 2004) at low risks of the methods involved. Three major factors affect the spontaneous probability of conception: time of unwanted non-conception, age of the female partner (Hunault et al., 2004
) and the cause of subfertility (Snick et al., 1997
). Before referral to a specialized centre for reproductive medicine or at the first consultation because of infertility problems, we (normally) only have the time of unwanted non-conception and the age of the women, on which we base our primary decision to act and to explore for causes of subfertility (with the risk of false-positive results) and then perhaps to start treatment. Or we encourage to wait.
In general, cumulative probabilities of conception decline with age but because of increasing heterogeneity in fecundity with age, the effects mainly depend on individual factors (Dunson et al., 2002; te Velde and Pearson, 2002
; Gnoth et al., 2003
; Dunson et al., 2004
) and may only be judged after a first infertility exploration.
Therefore, the duration of unwanted non-conception remains as the main factor indicating timing of investigation in case of a subfertility problem and it mainly defines the grades of subfertility and determines prevalence estimations. Based on the cited prospective TTP studies, we propose a simple, easy and memorable three-step grading for all day clinical use (Table I).
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References |
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Submitted on August 31, 2004; resubmitted on December 20, 2004; accepted on February 17, 2005.