Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities

BACKGROUND: In fertile populations, little is known about the association between semen parameters and time to pregnancy (TTP). METHODS: Pregnant women from Copenhagen, Edinburgh, Paris and Turku who conceived without medical intervention were asked for their TTP (942 couples), and their partners provided a semen sample. The proportion of morphologically normal sperm and the multiple anomalies index (MAI, ratio of the total number of anomalies to the number of abnormal sperm) were centrally estimated. We estimated rate ratios for the occurrence of a pregnancy by a discrete survival model, adjusted for sexual activity and female factors affecting fecundity. RESULTS: Increasing sperm concentration influenced TTP up to 55 x 10(6)/ml. The proportion of morphologically normal sperm influenced TTP up to 39% according to David's criteria, and this association held among the subjects with a sperm concentration >55 x 10(6)/ml. For strict criteria, the threshold value was 19% normal sperm. An increase of 0.5 in MAI was associated with an adjusted rate ratio for the occurrence of a pregnancy of 0.68 (95% confidence interval: 0.54-0.85). CONCLUSIONS: These results highlight the importance of sperm morphology parameters and indicate that the effect of proportion of normal sperm on TTP may be independent of sperm concentration.     

Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic

The sperm chromatin structure assay (SCSA) was used to measure over 500 human semen samples from two independent studies: Study I, 402 samples from 165 presumably fertile couples wishing to achieve pregnancy over 12 menstrual cycles; Study II, samples from 115 patients seeking fertility counselling. The SCSA measures susceptibility to DNA denaturation in situ in spermatozoa exposed to acid for 30 s, followed by acridine orange staining. SCSA data from the male partners of 73 couples (group 1) achieving pregnancy during months 1-3 of Study I were used as the standard of 'sperm chromatin compatible with high fertility' and were significantly different from those of 40 couples (group 3) achieving pregnancy in months 4-12 (P < 0.01) and those of male partners of 31 couples (group 4) not achieving pregnancy (P < 0.001). Group 2 contained couples who had a miscarriage. SCSA values for Study II were almost twice that of the Study I fertility standards. Within-couple repeatability tended to be less for group 3 than for groups 1, 2 or 4. Based on logistic regression, spermatozoa with denatured DNA (cells outside the main population, COMP alpha t) were the best predictor for whether a couple would not achieve pregnancy. Some 84% of males in group 1 had COMP alpha t < 15%, while no couples achieved pregnancy in group 1 with > or = 30% COMP alpha t, a threshold level considered not compatible with good fertility. Using selected cut-off values for chromatin integrity, the SCSA data predicted seven of 18 miscarriages (39%).     

Poor semen quality may contribute to recent decline in fertility rates

During past decades, we have witnessed a remarkable decline in fertility rates (number of births per 1000 women of reproductive age) in the industrialized world. It seems beyond doubt that the enormous social changes of our societies play the major role in this decline, but can it be attributed to changing social structures alone or is a reduced fecundity in the population also a factor? To address this we have focused on trends in teenage pregnancies (which to a large extent are unplanned). During the period in question fertility rates among 15-19 year old Danish women have been falling and the decline in fertility rate is not counterbalanced by an increase in the rate of induced abortion. When seen together with recent results from Denmark, which have shown that more than 30% of 19 year old men from the general population now have sperm counts in the subfertile range, we argue that this fall may not be attributable to social factors, changes in conception practices or diminished sexual activity alone. It seems reasonable also to consider widespread poor semen quality among men as a potential contributing factor to low fertility rates among teenagers. Due to the concern caused by the low sperm count among younger Danish men, the Danish Ministries of Health and Environment have launched a surveillance programme which includes an annual examination of the semen quality in 600 young Danes from the general population. We propose that researchers in other countries with low and falling fertility rates among young women should consider the possibility that semen quality of their younger male cohorts may also have deteriorated.     

Diurnal variation of semen quality in human males.

The possibility of a diurnal variation in semen quality was tested in 54 human males attending our infertility clinic. Of the enrolled subjects, 24 were normozoospermic and 30 were suffering from oligo- and/or asthenozoospermia. Seminal fluid was collected by masturbation twice by each subject, once in the morning (7:00-7:30 a.m.) and once in the afternoon (5:00-5:30 p.m.). Abstinence from sexual intercourse for 3-4 days before each of the two collections was requested. Semen parameters were evaluated independently by two biologists before and after pellet swim-up. Beside similar macroscopic parameters, specimens collected in the afternoon showed a higher number (P < 0.01) and concentration (P < 0.01) of spermatozoa. Also, immediately (P < 0.05), and at 1 h (P < 0.02) and 2 h (P < 0.01) after pellet swim-up, the number of spermatozoa with progressive linear motility was higher in the afternoon than in the morning. These data are the first documenting a diurnal rhythm in sperm quality which may contribute to the reported variability in semen parameters, and may prove useful for spontaneous and assisted conceptions.     

Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation.

BACKGROUND: In order to provide a reference for infertile men, we defined normal values of semen quality in a population of fertile men, using computer-assisted semen analysis (CASA) before and after sperm separation. Additionally, we investigated the relationship between semen quality and time to pregnancy (TTP). METHODS AND RESULTS: Semen samples were obtained from 315 proven fertile men. The median sperm concentration in fresh samples was 107 x 10(6)/ml (5-95 percentiles: 16-322 x 10(6)/ml), the median percentage of motile sperm cells was 65% (14-87%) and the median percentage of progressively motile cells was 37% (5-64%). After density gradient sperm separation, the median total sperm count was 46 x 10(6) (4-350 x 10(6)), the median percentage of motile sperm cells was 77% (16-95%) and the median percentage of progressively motile cells was 63% (11-84%). No significant associations were found between TTP and sperm counts or sperm motility, either before or after sperm separation. This may be due in part to the fact that the study comprised couples with proven fertility. CONCLUSION: We have defined semen parameters, including the results of density gradient separation, in a population of normal fertile men which may be of interest in the evaluation of semen samples from infertile men.     

Increased expression of secretory actin-binding protein on human spermatozoa is associated with poor semen quality

BACKGROUND: Antibodies to human sperm are useful diagnostic reagents for detection of changes in sperm protein expression and their relationship with sperm defects and male infertility. The specificity of Hs-16 monoclonal antibody (mAb) and the localization and frequency of the occurrence of Hs-16-recognized protein on human spermatozoa were investigated. METHODS: Samples from 30 fertile men with normal spermiograms and 30 men with pathological spermiograms were studied. The specificity of Hs-16 mAb was analysed by the western blotting technique and matrix-assisted laser desorption/ionization mass spectrometry. Indirect immunofluorescence with Hs-16 antibody was used to test sperm ejaculates. RESULTS: The Hs-16 antibody detected a human sperm and seminal plasma protein, which was determined to be secretory actin-binding protein (SABP). This specificity was also verified by co-localization of SABP and actin on spermatozoa with Hs-16 and anti-actin antibodies, and partial co-localization of these proteins was found. SABP was localized on the sperm tail, mainly in the midpiece of the tail. Other parts of spermatozoa were labelled with lower frequency. A significant difference was found in SABP labelling between men with normal spermiograms and donors with asthenozoospermia or oligoasthenoteratozoospermia (both P < 0.01), and asthenozoospermia versus oligoasthenoteratozoospermia (P < 0.05). Increased expression of SABP was observed in men with pathological spermiograms. CONCLUSIONS: Hs-16 antibody reacts specifically with SABP. SABP can serve as a marker of defective sperm and may be associated with fertility failure.     

Time trends in waiting time to pregnancy among Danish twins

BACKGROUND: Little is known about time trends in fecundity because few population-based data are available. In a survey among female twins born from 1953 to 1976, their time to pregnancy did not differ from singletons and can be considered to represent the fecundity of the general population. METHODS: Information was collected by interview about waiting time to first pregnancy (TTP) and any periods of subfecundity among both male and female twins born between 1931 and 1952. Trends were analysed by considering the year of birth of the index person (birth cohort effect) or year at which the first attempt started (period effect). RESULTS: Eighty-five percent of male and 81.3% of female eligible twins participated. A total of 1598 male twins and 1653 female twins reported a TTP value and 1671 men and 1715 women had a value for their first attempt to conceive including unsuccessful attempts. No overall trends in either male or female TTP were observed with increasing year of birth or of starting time, after adjustment for confounders, but for attempts fecundity increased among female twins by year of birth or of starting the attempt. A decreasing risk of severe infertility with increasing year of birth or year for start of the attempt was observed among male twins, but this observation was based on only 81 men and was not seen among female twins. CONCLUSION: No decreasing trend in fecundity was observed among Danish twins born between 1931 and 1952 who had completed their reproduction. Female twins had a slight increase in fecundity, and men a decrease in severe infertility. In addition, TTP was apparently well reported and recalled for up to 50 years among both male and female twins.     

The impact of cigarette smoking on human semen parameters and hormones

BACKGROUND: In this prospective study, semen parameters and hormone concentrations of infertile smokers were compared with infertile non- and ex-smokers. We also determined how many men with idiopathic infertility would stop smoking in an attempt to improve their fertility. METHODS: 1104 men (517 non-smokers, 109 ex-smokers and 478 smokers) with infertility for at least 1 year were evaluated. Evaluation included medical history, physical examination, hormone analysis and two semen analyses. Prior to the second semen analysis, smokers were urged to quit smoking. RESULTS: Smokers were significantly younger (P < 0.001), had significantly more round cells in their ejaculates (P = 0.003), and the percentage of ejaculates with > 1 x 10(6)/ml leukocytes was higher in smokers (P < 0.001). Increased free and total serum testosterone (P < 0.001) and decreased prolactin levels (P < 0.001) were found in smokers. No differences were found between non-smokers and ex-smokers. Only 23.1% of the smokers versus 46% non-smokers (P < 0.001) returned for a second semen analysis, 14 of whom reduced and 15 of whom quit smoking completely. Testosterone levels were significantly lower in those who were able to stop or reduce smoking (P < 0.001). CONCLUSIONS: Smoking does not affect conventional semen parameters, but significantly increases round cells and leukocytes. Only a few idiopathic infertile smokers were able to quit smoking.     

The value of sperm swimming speed measurements in assessing the fertility of human frozen semen

The purpose of this study was to evaluate relationships betweenmeasured sperm velocity and in-vivo fertility, using donor semensamples from an artificial insemination (AID) programme. Seventy-onefrozen semen samples were examined; measurements of sperm velocitywere made immediately after thawing, upon a motile ’swim-up‘fraction, and finally after 3.5 h incubation at 37°C inthe freezing mixture. Zona-free hamster egg penetration assayswere performed upon all samples. Two groups of samples wereidentified; seven donors (11 samples) had failed to produceany pregnancies through AID from a range of 3 to 14 cycles tested,whilst the remaining samples (from 25 donors) had achieved atleast one pregnancy each. The mean sperm velocity (±SEM) for the latter ’fertile‘ group was significantlyhigher than the corresponding value for the ’infertile‘group; (i) after thawing, 65.9 ± 1.8 versus 50.4 ±3.2 µm/s (P < 0.001) and (ii) after 3.5 h incubation,42.1 ± 2.1 versus 24.7 ± 5.7 µ/s (P <0.002). Using the maintenance of sperm velocity during incubationas an indicator of survival, life-table analyses were used tocalculate monthly conception rates on various sub–groupsof the semen samples. Poor survival (>40% decline in velocityover 3.5 h) was associated with a monthly pregnancy rate ofonly 11.58% (362 cycles), whilst better survival ( < 40%decline) was associated with the significantly higher (p = 0.024)pregnancy rate of 16.87% (480 cycles)     

Studies of HLA, fertility and mate choice in a human isolate.

The role of human leukocyte antigen (HLA) genes in pregnancy and in human mate choice has been investigated in the Hutterites, an inbred population of European origins. High-resolution HLA haplotypes were defined by alleles at 16 loci in >1000 Hutterites. Prospective studies of pregnancy outcome previously demonstrated increased fetal loss rates among Hutterite couples matching for HLA-B antigens (P = 0.033) or for the entire 16-locus haplotype (P = 0.002). Among living children of couples matching for HLA-B or for the haplotype, there was a non-significant deficit of children who were heterozygous and compatible with the mother; the number of living children who were compatible and homozygous or incompatible and heterozygous was not different than expectations (HLA-B, P = 0.095; haplotype, P = 0.376). Mate choice among 411 couples was non-random with respect to the HLA haplotype, assessed by a variety of methods (P = 0.020 to <0.001). These combined data indicate a role for HLA region genes in both pregnancy outcome and mate choice, and suggest that selection acting on these genes occurs pre-conceptually as well as during pregnancy. This review outlines previously published studies on HLA, fertility and mate choice in the Hutterites.     

Lead, magnesium, selenium and zinc in human seminal fluid: comparison with semen parameters and fertility

The concentrations of lead, magnesium, selenium and zinc inseminal fluid from men with variable semen quality (sperm morphology,density and motility) and fertility were determined by atomicabsorption spectrometer without or with Zeeman background correction.The mean (?SD) concentration of selenium in the samples (n =142) was 28.8 ? 9.5 µg/l, which was about a third of thecorresponding serum value (77.8 ? 13.3 µg/l, n = 140).The serum selenium level was significantly (P < 0.001) higherin infertile than in fertile men, but the seminal fluid didnot show such a difference. No correlation was obtained betweenselenium values in seminal plasma and sperm density or motility.The levels of lead in seminal fluid were very low with no correlationto the levels of magnesium, selenium and zinc or the semen qualities.The seminal fluid lead concentration was significantly (P <0.001) higher in infertile (3.6 ? 3.2 µg/l, n = 79) thanin fertile men (1.7 ? 1.0 µg/l, n = 39). Magnesium (103.5? 49.2 mg/l, n = 90) and zinc (141.1 + 71.7 mg/l, n = 157) concentrationsin seminal fluid were comparable with previous reports. Bothminerals showed a positive correlation to the seminal fluidselenium, while only zinc displayed a borderline correlationwith sperm density. The present findings indicate that the determinationof seminal fluid selenium may not offer any advantages overzinc and magnesium measurement in the fertility assessment andits role in human semen remains obscure. The low lead concentrationsin the present material is a clear indication of low industrialexposure.     

Subsequent fertility for patients presenting with an ectopic pregnancy and having an intra-uterine device in situ.

Of 503 ectopic pregnancies (EP) dealt with surgically using conservative laparoscopic techniques, 153 (30.4%) occurred in patients with an intra-uterine device (IUD) in situ. Examination of the characteristics of the EP revealed that the fimbrial location was more frequent among patients with an IUD whereas a significantly higher proportion were located in the isthmus in the group of patients without an IUD. Whereas the condition of the tubal wall did not differ according to the presence or absence of an IUD, adhesions and obstructed or non-existent contralateral tubes were significantly less frequent among patients with an IUD in situ. Two hundred and twenty three patients desired pregnancy, 30 of whom had an IUD in situ when the EP was diagnosed. The subsequent fertility for these 30 patients with an IUD was shown by rates for intrauterine pregnancy (IUP), recurrent EP and infertility of 96.7, 3.3 and 0% respectively. These results were significantly better than those for women who had no IUD, the figures for this group being 59, 13.4 and 27.4%, respectively. The favourable prognosis was due solely to the fact that women with an IUD had far fewer negative antecedents and that the EP probably occurred due to impaired ciliary action which is reversible when the IUD is removed.     

Psychological factors in the aetiology of infertility: a prospective cohort study

The objectives were to identify and measure psychological factorscharacterizing the period following the cessation of contraceptionand to assess these psychological factors as predictors of thecouples' fertility. A cohort of 63 couples with initially undeterminedfertility status was prospectively studied, first shortly afterthe cessation of contraception, then 13 months later. The ChildProject Questionnaire was constructed to assess psychologicalvariations following the cessation of contraception. An InterspouseDifference Score was constructed to measure the difference betweenthe spouses' responses. Three male and three female factorswere derived from the questionnaire. The Interspouse DifferenceScore was significantly greater in infertile than in fertilecouples. Two psychological factor scores were significantlyhigher in fertile subjects: the wives' level of positive expectationsrelated to motherhood, and the husbands' quality of integrationbetween the wish for a child and sexual relationships. Withinthe group of fertile couples, time to pregnancy was predictedby the husbands' above-cited factor and by the wives' frequencyof thoughts and concerns related to the desired child. The resultssupport the conclusion that in both women and men, psychologicalfactors specifically related to the project of conceiving achild are significant predictors of the couple's fertility status.     

Hepatocyte growth factor in human semen and its association with semen parameters

Hepatocyte growth factor (HGF) is a structurally unique growth factor with potent motogenic (motility inducing) effects. Studies in the murine male genital tract have suggested important associations between HGF and the acquisition of sperm motility during epididymal maturation. The aim of this study was, therefore, to determine the concentration of HGF in human semen and assess its correlation, if any, with sperm motility and other semen parameters. Semen samples were collected by masturbation and analysed using standard procedures. HGF concentrations were measured in duplicate using an enzyme-linked immunoassay technique. Total protein estimations were also made in a subset of samples. The 95 subjects were divided into three groups for analysis: normozoospermic, subnormal semen and azoospermic. HGF was detected in all samples (median 0.456, 25th centile 0.388, 75th centile 0.556 ng/ml). No significant correlations were found between semen HGF concentrations and sperm concentration, motility, total sperm count or total motile count. There were no significant differences in mean HGF concentrations between the three subgroups. In conclusion HGF is present in human semen in significant quantities. The data do not suggest HGF concentrations are correlated with parameters of sperm motility.     

Menses, fertility and pregnancy after arterial embolization for the control of postpartum haemorrhage

BACKGROUND: The long-term effects of uterine artery embolization for the control of postpartum haemorrhage on menses, fertility and future pregnancy evolution have not been assessed. METHODS: Between November 1993 and July 1999, 31 women with obstetric haemorrhage underwent arterial embolization. Four patients underwent a hysterectomy. Gynaecological information on 25 of the 27 patients who did not undergo hysterectomy was obtained by interview. RESULTS: All women had a return of normal menses. Nine of the 25 patients desired subsequent pregnancy and five patients became pregnant with normal delay of conception. Moreover, two other patients who did not plan another pregnancy became pregnant. A total of 10 pregnancies was studied, four ended during the first trimester. For the six others, the maternal evolution of the pregnancy was uneventful until term. No case of pre-eclampsia was observed. The ultrasonographic examinations revealed normal fetal growth and umbilical and uterine Doppler studies showed no anomaly. No repetition of obstetric haemorrhage was observed. All full-term, newborns were healthy, weighing from 3220 to 4100 g. CONCLUSION: Our results suggest that women who undergo arterial embolization for obstetric haemorrhage should expect to have a return of normal menses with preservation of future fertility and successful uneventful pregnancies.     

Gender-specific association of the factor V Leiden mutation with fertility and fecundity in a historic cohort. The Leiden 85-Plus Study

BACKGROUND: Factor V Leiden (FVL, Arg506Gln) mutation may facilitate embryo implantation and increase fertility and fecundity. This was studied in subjects who were of childbearing age in a time with minimal fertility control without modern contraceptive methods. METHODS: From 1986 to 1999, 1502 inhabitants of Leiden, The Netherlands, reaching the age of 85 years were enrolled in the Leiden 85-Plus Study. Of 1176 subjects the FVL status was analysed, in 365 male and 811 female subjects. RESULTS: The FVL carrier rate was 4.3%. Fertility was not affected by FVL status. In male subjects, fecundity (interval between marriage and birth of first child) was significantly increased in FVL carriers; 67% of male FVL carriers had a child within 371 days of marriage (therefore conceived within 3 months of marriage), compared with 19% of male non-carriers [relative risk (RR), 3.5; 95% confidence interval (CI), 2.1-5.7; P < 0.001]. Within 6 months of marriage, 75% of male FVL carriers had conceived a child compared with 34% male non-carriers (RR, 2.2; 95% CI, 1.5-3.2; P = 0.01). In female subjects, fecundity was not influenced by FVL status. CONCLUSION: Fecundity is increased in male FVL carriers; in female subjects, no such association was observed.     

Decreased human semen quality and organochlorine compounds in blood

BACKGROUND: Various studies have been performed in which potential effects of xenoestrogens on fertility or sperm parameters were investigated by comparing groups of subjects exposed to different levels of these chemicals. METHODS: In our study we used an alternative approach, as we selected one group of men with very poor semen quality and another group with normal semen quality and determined the blood organochlorine contents in order to determine whether a difference in these levels could be established. Organochlorine compounds, including polychlorinated biphenyls (PCB) and PCB metabolites, were detected using gas chromatography. The concentrations were compared between both groups, and related to semen parameters. RESULTS: A comparison of both groups did not reveal significant differences in organochlorine levels. Linear relationships were found when PCB and metabolite concentrations were related to the age of the volunteers. Focusing on the subgroup of men with normal semen quality showed that sperm count and sperm progressive motility were inversely related to the concentrations of PCB metabolites within this group. CONCLUSIONS: The finding of a significantly decreased sperm count in relation to an elevated PCB metabolite level within the subgroup of men with normal semen quality is important. This is the first time that a correlation between exposure to environmental pollutants with endocrine-disrupting capacity and human sperm quality has been observed.     

Different perspectives of patients and health care professionals on the potential benefits and risks of blastocyst culture and multiple embryo transfer

BACKGROUND: A trade-off exists between the risk of multiple pregnancy and prospects of pregnancy itself in assisted reproduction. Blastocyst culture and embryo transfer after approximately 5 days may be one method of reconciling this dilemma, although a controversial one. METHODS AND RESULTS: We presented a questionnaire to groups of patients, embryologists and clinicians to solicit views on the potential benefits and risks of blastocyst culture and multiple pregnancy. The results indicate that patients are more accepting of multiple pregnancy as a prospective outcome of treatment than those involved in their treatment, despite awareness of the risks. Our data tend to support a genuine difference in values on this point. We also sought views on the patient selection criteria and treatment protocols which should apply in a planned randomized controlled trial comparing blastocyst culture with cleaving embryo transfer (e.g. numbers of embryos to transfer, acceptable levels of risk of twin and triplet pregnancy, the proportion of patients who would be put off from entering the trial by the risk of no embryo transfer). These are presented and discussed with reference to their likely impact on trial recruitment, highlighting differences in perspective between patients and professionals. CONCLUSIONS: We conclude that there are differences among patients, embryologists and clinicians in their perceptions of the desirability of multiple pregnancy, their preferences in certain practical aspects of treatment such as embryo transfer numbers, and their ideas on blastocyst culture and its prospective outcomes and risks.     

Recruitment and motivation of semen providers in Sweden

BACKGROUND: Legislation in Sweden requires that semen providers are prepared to be identified to offspring (at maturity) should this be requested. This study presents views of semen providers in Sweden regarding factors associated with their recruitment and motivation. METHODS: All semen providers (n = 30) in two clinics in different parts of Sweden participated in a questionnaire survey and both quantitative and qualitative data are reported. RESULTS: While there were some important demographic differences between the two clinic populations, there was total agreement that the desire to assist infertile couples was the sole or main motivating factor in becoming a semen provider. Monetary reward was not reported by respondents to be an important motivator, although at least 50% of the providers in both clinics thought that payment should be made and reimbursement of expenses was reported as being important. Men responded to both advertising and personal experiences or contacts they had with infertile couples. The involvement and support of the semen provider's partner was regarded as important. CONCLUSIONS: Semen providers can be recruited within a system that requires them to be prepared to be identified to offspring in the future. The characteristics of such providers vary, but are typified by a strong desire to assist infertile couples.     

Definition and prevalence of subfertility and infertility

A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.