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Épidémiologie de l’infertilité
Abstract
L’infertilité est, depuis plusieurs années, considérée par l’Organisation médicale de la santé comme une pathologie à part entière, dans le cadre du concept de santé reproductive qui reconnaît à chaque être humain le droit à la procréation (1). Elle est le siège de nombreux enjeux de société, et tout ce qui la concerne est fortement médiatisé, notamment les facteurs environnementaux et les traitements d’assistance médicale à la procréation. Cependant, ses contours restent souvent flous, sa fréquence difficile à mesurer, ses causes nombreuses. Par ailleurs, elle s’inscrit dans un contexte mondial de diminution des naissances dans lequel il n’est toujours aisé, en ce qui concerne les données démographiques, de séparer l’infertilité involontaire de la diminution volontaire des projets familiaux, mais aussi dans celui de l’augmentation de l’AMP et de l’âge des couples qui cherchent à procréer. L’objectif de ce chapitre sera donc : (1) de rappeler les concepts scientifi ques sous-jacents à la mesure de la fertilité et de l’infertilité, (2) de faire le point sur sa fréquence de par le monde et (3) de déterminer les facteurs mis en cause.
... This situation concerns 15% of couples who desire to procreate. In Central Europe, its prevalence varies between 10% -15% [3] [4]. In Cameroon as in Africa, 20% to 30% of couples suffer from infertility [1] [3]. ...
... In Central Europe, its prevalence varies between 10% -15% [3] [4]. In Cameroon as in Africa, 20% to 30% of couples suffer from infertility [1] [3]. Despite the advances in Assisted Reproductive Technology (ART), couple infertility in our context remains a source of anxiety and even rejection within the family. ...
Menopause is triggered by the number of ovarian follicles falling below a threshold number and is irreversible because oogonial stem cells disappear after birth. Since it is the result of programmed disappearance of a limited store of follicles, menopause can be predicted using mathematical models based on total follicle counts at different ages. Our model shows follicle numbers decline bi-exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of -0.097 and a second of -0.237. The change occurred when numbers had fallen to the critical figure of 25,000 at age 37.5 years. The unexpectedly faster rate of ovarian ageing afterwards lowers the follicle population to 1000 at approximately 51 years, and was adopted as the menopausal threshold because it corresponds to the median age of menopause in the general population. Had the earlier rate persisted menopause would not be expected until 71 years. The impact of step reductions of follicle numbers on the prospective span of menstrual life was predicted by the model. A reduction by 50% before age 30 years resulted in the threshold being reached at 44 years and 0.6 year later for every subsequent year until age 37.5 years after which it is reached at 48 years. A reduction of 90% in childhood before age 14 years could result in menopause as early as 27 years, with increments of 0.6 year per year afterwards until after 37.5 years when it is expected at age 41 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Several studies published within the past 10 years indicate that smoking reduces fecundity, but not all studies have found this effect, and smoking cessation is not used routinely in infertility treatment in Europe. The present study was designed to examine male and female smoking at the start of a couple's waiting time to a planned pregnancy. Two types of samples were used: population-based samples of women aged 25-44 years who were randomly selected in different countries from census registers and electoral rolls, in which the unit of analysis was the couple; and pregnancy-based samples of pregnant women (at least 20 weeks' pregnant) who were consecutively recruited during prenatal care visits, in which the unit of analysis was a pregnancy. More than 4,000 couples were included in each sample, and 10 different regions in Europe took part in data collection. The data were collected between August 1991 and February 1993 by personal interview in all population-based samples and in all but three regions of the pregnancy sample, where self-administered questionnaires were used. The results based on the population sample showed a remarkably coherent association between female smoking and subfecundity in each individual country and in all countries together, both with the first pregnancy (odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.3-2.1, at the upper level of exposure) and during the most recent waiting time to pregnancy (OR = 1.6, 95% CI 1.3-2.1). Results based on the pregnancy sample were similar (OR = 1.7, 95% CI 1.3-2.3). No significant association was found with male smoking (in the population sample, OR = 0.9, 95% CI 0.7-1.1 (first pregnancy) and OR = 1.0, 95% CI 0.9-1.3 (most recent waiting time); in the pregnancy sample, OR = 0.9, 95% CI 0.7-1.1). The fecundity distribution among smokers appeared to be shifted toward longer waiting times without a change in the shape of the distribution. Women who have difficulty conceiving should try to stop smoking or to reduce their smoking to less than 10 cigarettes per day.
During 1992-1995, 430 Danish couples were recruited after a nationwide mailing of a letter to 52,255 trade union members who were 20-35 years old, lived with a partner, and had no children. The couples were enrolled into the study when they discontinued birth control, and they were followed for six menstrual cycles or until a clinically recognized pregnancy. At enrollment and each month throughout the follow-up, both partners completed a questionnaire that asked them about their smoking, alcohol consumption, and intake of caffeinated beverages. The effect of current smoking and smoking exposure in utero was evaluated by using a logistic regression model with pregnancy outcome of each cycle in a Cox discrete model calculating the fecundability odds ratio. After adjustment for female body mass index and alcohol intake, diseases in female reproductive organs, semen quality, and duration of menstrual cycle, the fecundability odds ratio for smoking women exposed in utero was 0.53 (95% confidence interval (CI) 0.31-0.91) compared with unexposed nonsmokers. Fecundability odds ratio for nonsmoking women exposed in utero was 0.70 (95% CI 0.48-1.03) and that for female smokers not exposed in utero was 0.67 (95% CI 0.42-1.06). Exposure in utero was also associated with a decreased fecundability odds ratio in males (0.68, 95% CI 0.48-0.97), whereas present smoking did not reduce fecundability significantly. It seems advisable to encourage smoking cessation prior to the attempt to conceive as well as during pregnancy.
The objective of this study was examine geographical variation in couple fecundity in Europe. The study was based upon all recently pregnant (or still pregnant) women within well-defined geographical areas in Europe (Denmark, Germany, Italy, Sweden and France) at a given time period in 1992. Altogether, 4035 women responded to a highly structured questionnaire. Highest fecundity was found in Southern Italy and Northern Sweden; lowest fecundity was seen in data from the East German centre. Approximately 16% of the study population had a waiting time of more than 12 months to become pregnant. Most of the pregnancies were planned (64%) and approximately 14% were the result of contraceptive failures. The study shows that smoking, body mass index, age and parity did not explain the differences in fecundity found between the centres. Regional differences in fecundity exist and the causes may be genetic or due to variations in behavioural and environmental exposures.
In fertile populations, little is known about the association between semen parameters and time to pregnancy (TTP).
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.
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).
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.
It is well known that miscarriage risk increases with age. However, studies usually investigate only maternal age effects. We investigated both maternal age and paternal age effects on miscarriage risk to provide insight into this frequent reproductive failure.
The last planned pregnancies (n = 3174) that ended in a birth or miscarriage were analysed in a retrospective population-based study on women aged 25-44 years in Denmark, Germany, Italy and Spain. Maternal and paternal ages were analysed together, using a single variable 'couple age' in a multivariate logistic regression analysis, with couples composed of a woman and a man both aged 20-29 years forming the reference group.
After adjustment for various factors (e.g. reproductive history, country), we found that the risk of miscarriage was higher if the woman was aged > or = 35 years, as has already been reported in a number of studies. However, the increase in risk was much greater for couples composed of a woman aged > or = 35 years and of a man aged > or = 40 years. Potential source of bias (especially 'reproductive compensation') are discussed.
The risk of an adverse pregnancy outcome is highest if both partners are advanced in age.
BACKGROUND. Although paternal age may be a risk factor for reproductive failure, unlike maternal age it has received little attention. We reviewed the existing literature, analyzing the effect of paternal age on two main reproductive failures: infertility and miscarriage. METHODS. We searched MEDLINE with the keyword “paternal age” and checked the exhaustiveness of our list of references. RESULTS. We found that published studies provided evidence that increasing paternal age could be a risk factor for reproductive failure. Several studies indicated that the risk of infertility increases in men in their late thirties. Furthermore, increased risk of miscarriage and late fetal deaths has been found when fathers were aged 35-40 years and over. CONCLUSIONS. The age of 40 years may be the male equivalent of the so-called “amber light” at 35 years in the reproductive life of women. Confirmation of the existence of a “cut-off age” in male fertility requires further investigation in large scale studies.
The purpose of this study was to examine the risk of infertility that is associated with paternal age, because this factor rarely has been investigated, whereas maternal age of >or=35 years is a well-known risk factor.
This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993.
Among couples composed of a woman aged 35 to 39 years, risks were significantly higher when paternal age was >or=40 years than when paternal age was <40 years, with an adjusted odds ratio of 2.21 (95% CI, 1.13, 4.33) for delay in pregnancy onset (failure to conceive within 12 months) and of 3.02 (95% CI, 1.56, 5.85) for difficulties in having a baby (failure to conceive within 12 months or pregnancy not resulting in a live birth).
Like maternal age of >or=35 years, paternal age of >or=40 years should be considered to be a key risk factor for infertility.
Cigarette smoking (CS) is a widely recognized health hazard, yet it remains prevalent in society and the effects of environmental tobacco smoke exposure on fertility are unknown. Our objective was to measure the effects of CS on the fertility of mainstream (MS) or sidestream (SS) smoke-exposed women compared to their non-smoking (NS) counterparts.
This retrospective study investigated 225 female patients undergoing IVF (n = 97) or ICSI (n = 128). Patients were grouped based on their smoking status for comparison. This included: 39 MS (18 IVF and 21 ICSI); 40 SS (16 IVF and 24 ICSI); and 146 NS (63 IVF and 83 ICSI) women. Fertility treatment outcomes including embryo quality, implantation and pregnancy rate were measured.
No difference in embryo quality between the three groups was observed. However, there was a significant difference in implantation rate (MS = 12.0%, SS = 12.6%, and NS = 25.0%) and pregnancy rate (MS = 19.4%, SS = 20.0%, and NS = 48.3%) per embryo transfer.
Despite similar embryo quality there was a striking difference in implantation and pregnancy rates of MS and SS smokers when compared with NS. Our data demonstrate that the effects of SS smoking are equally as damaging as MS smoke on fertility.
Recent findings have indicated that prenatal exposure to tobacco smoke may cause lower sperm concentration in ejaculates of adult men. To extend the research on this hypothesis we investigated the dose-dependency of the association, controlling for other prenatal exposures.
From 1987 to 1996, four separate occupational semen studies were conducted at three centres in Denmark. A total of 945 men provided semen and blood samples, and information on reproductive and lifestyle factors. In 2004, we collected data on the maternal smoking habits during pregnancy from 522 mothers of the participating men.
Adjusting for study subgroup, abstinence time and other factors, we found statistically non-significant differences in mean sperm concentrations: 65.0 x 10(6)/ml [95% confidence interval (CI) 51, 81] among sons of non-smokers; 59.1 x 10(6)/ml (95% CI 46, 75) among sons of mothers who had smoked 1-10 cigarettes/day; and 57.7 x 10(6)/ml (95% CI 40, 81) among those whose mothers had smoked >10 cigarettes/day. The former group had a higher odds ratio (OR) for oligozoospermia (sperm concentration < or =20 x 10(6)/ml) of 1.5 (95% CI 0.9, 2.8), the latter group an OR of 2.6 (95% CI 1.2, 5.8).
We observed a dose-dependent association between prenatal tobacco exposure, lower sperm concentration and higher risk of oligozoospermia.
To investigate paternal age effect mediated by biological modifications with use of data from assisted reproductive technologies.
National IVF registry.
Fifty nine French IVF centers.
A total of 1,938 men whose partners were totally sterile, with bilateral tubal obstruction or absence of both tubes (to avoid bias sampling in analysis of paternal age) and treated by conventional IVF.
None.
Risk of failure to conceive defined as absence of intrauterine pregnancy.
The odds ratio of failure to conceive for paternal age > or =40 years was 2.00 (95% confidence interval [CI]: 1.10-3.61) when the woman was 35-37 years old, 2.03 (95% CI: 1.12-3.68) for age 38-40 years, and 5.74 (95% CI: 2.16, 15.23) for age 41 years and over.
As an increasing number of couples choose to postpone childbearing, they should be informed that paternal age over 40 years is an important risk factor for failure to conceive.
The aim of this study was to investigate the prevalence of infertility and the use of infertility treatment among women aged 40-55 years.
Population-based postal questionnaire survey of UK women. Over 60,000 women randomly sampled from the 2001 electoral roll were sent a questionnaire, and those aged 55 years and under who had ever been pregnant or tried to achieve a pregnancy (n = 6584) were asked to provide a reproductive history.
Overall, 2.4% of women aged 40-55 years had unresolved infertility with no pregnancies, and a further 1.9% had been pregnant but not achieved a live birth. The prevalence of unresolved fertility did not differ among birth cohorts. Sixteen percent of women reported ever consulting a doctor because of infertility and 8% reported receiving treatment to conceive. Across the whole sample, 4.2% of women reported that they had achieved at least one pregnancy as a result of treatment. Compared with earlier birth cohorts, women born later were more likely to report consultations (18% versus 13%) and treatment (9% versus 6%) for infertility, and pregnancies as a result of infertility treatment (6.7% versus 2.7%). Among those who reported medical consultations, women born more recently first consulted at a later age compared with those born earlier.
Although both the number of women seeking medical care for infertility and the proportion reporting pregnancies as a result of infertility treatment has increased, there is no evidence to support an overall increase in unresolved infertility over the past 15 years. The vast majority of women aged 40-55 who reported difficulties conceiving did have a child, or children, at some point in their lives.
An analysis of the influence of women's age on the results of in-vitro fertilization was performed, using 5590 attempts collected during the year 1986. Increasing age was found to be related to decreased success rates from 19.8% per attempt below the age of 25 years, to 9% per attempt at 40 years or more. A cut-off point was found between the ages of 36 and 37 years, using a mathematical model. The decrease was related to a reduction in oocyte production (4.3 ± 2.8 at 25 years or less and 3.3 ± 2.1 at 40 years or more, P > 0.001), and to a reduced implantation rate, whatever the number of transferred embryos. These findings were not due to spouse's age, rank of attempt, infertility diagnosis or oocyte stimulation regimen, since the effect of age remained significant when a logistical model including these confounders was applied. Finally, a woman's age must be considered as a prognostic factor when IVF is proposed to infertile couples.
Reproductive failure occurs in all forms of life, plant and animal. I have been asked to make a few introductory or general remarks about the problem in man. Whatever I have to say is based upon 35 years’ experience in obstetric and gynecologic pathology, seasoned by interest in the early embryology of the human and interspersed with a nine-year interval as clinical obstetrician. These remarks are in no sense an exhaustive review of reproductive anatomy, physiology and pathology, even as applied to the human, let alone to mammals in general. Comments will be confined to my observations on the early or potentially abortive phases of human development and a pathologic evaluation of a thousand consecutive human abortions, most of them spontaneous.
How much does the capacity to reproduce decline with age? Until quite recently, it was believed that fecundity declined slightly from age 20 to the early thirties, but more sharply after 35. Then a French study (Federation CECOS, 1982) published in February, 1982, reported results from a group of women who had undergone artificial insemination (Table I). Approximately 74% of women who were not over 30 conceived within 12 menstrual cycles. The percentage fell to only 62 for women 31–35, and to 56 for women 36–40. An accompanying editorial and many later newspaper and magazine articles suggested that risks of infertility rose sharply starting as early as age 30. The purpose of this chapter is to review evidence of the level and age pattern of decline in fecundity for women and for men and then to focus on delayed childbearing.
Dans de nombreux pays à forte fécondité, et dans certaines cohortes au sein des pays industrialisés à basse fécondité, la proportion des couples restant inféconds (aucune naissance vivante) en fin de période reproductive ne dépasse pas 5%. On peut donc penser que la proportion de couples restant involontairement inféconds est généralement inférieure à cette valeur. L'enquête effectuée en France par l'INED et l'INSEE en 1978 confirme ce résultat, mais elle montre aussi que près d'un couple sur cinq rencontre, à un moment ou un autre, des difficultés pour concevoir. Ces difficultés sont dans la grande majorité des cas surmontées, et elles se traduisent seulement par un allongement (en moyenne très significatif) du délai de conception. Face à de tels problèmes, la femme consulte un médecin dans 6 cas sur 10, et l'homme dans 2 à 3 cas sur 10. Au total, la stérilité et l'hypofertilité pourraient réduire de 2 à 7% la fécondité totale. /// In many countries in which fertility is high and in some cohorts in industrialized countries with low fertility, the proportion of couples who have not produced a live child by the end of the reproductive period does not exceed five per cent. It could, therefore, be concluded that the proportion who are involuntarily sterile is lower than this value. A survey carried out in France by INED and INSEE in 1978 confirms this result, but it is also found that nearly one couple in five experiences difficulty in conceiving at some time during their reproductive lives. In most cases, these difficulties can be overcome and result only in increasing (on average very substantially) the period of conceptive delay. Six out of every ten women who are faced with such problems take medical advice, as do between 20 and 30 per cent of men. Sterility and sub-fecundity probably reduce total fertility by between two and seven per cent. /// En numerosos países de alta fecundidad y en ciertas cohortes en el seno de países industrializados de baja fecundidad, la proporción de parejas que terminan infecundas su período reproductivo (sin ningún nacido vivo), no sobrepasa un 5%. Puede pensarse entonces que la proporción de parejas que permanecen involuntariamente infecundas es en general inferior a esta proporción. La encuesta realizada en Francia por el INED en colaboración con el INSEE, en 1978, confirma este resultado. Esta encuesta muestra también que aproximadamente una pareja sobre cinco encuentra dificultades para concebir en uno u otro momento de su vida. Estas dificultades son superadas en la mayoría de los casos, y se traducen solamente en un alargamiento del intervalo de concepción (a veces muy significativo). Frente a este tipo de problemas la esposa consulta un médico en 6 casos sobre 10 y el esposo en 2 o 3 casos sobre 10. En el conjunto, la esterilidad y la subfertilidad podrían reducir la fecundidad total en proporciones que fluctuan entre un 2 y un 7%.
La proportion de femmes de 25-44 ans déclarant avoir eu des difficultés pour concevoir a fortement progressé de 1978 à 1988, passant de 18 à 30%. En moyenne, elles ont attendu un peu moins de deux ans pour être enceintes, et ce délai ne paraît pas avoir changé d'une date à l'autre. Si l'on exclut les délais inférieurs ou égaux à 12 mois, la proportion de femmes "hypofertiles" tombe de 30 à 17% (en 1988), ce qui constitue un pourcentage encore élevé et probablement assez proche de celui des couples qui sont amenés à consulter un médecin pour "stérilité" au moins une fois dans leur vie. La plus forte proportion de difficultés déclarées en 1988 par rapport à 1978 pourrait résulter d'une plus grande impatience des couples interrogés en 1988, et surtout d'une moindre résignation de ceux-ci par rapport à ceux interrogés en 1978; il n'est donc pas certain qu'il y ait eu une progression réelle de l'hypofertilité ou de la stérilité. /// The proportion of women between the ages of 25 and 44 who admitted to having experienced difficulty in conceiving, sharply increased between 1978 and 1988, rising from 18% to 30%. They had waited, on average, slightly less than two years to conceive, a period which does not seem to have changed over time. If durations of 12 months or less are excluded, the proportion of "sub-fecund" women drops from 30% to 17% which is still a high percentage, very similar to that of couples who are led to consult a physician for "sterility" problems at least once in their lifetime. The increased proportion of difficulties expressed in 1988 compared with 1978 could be the result of greater impatience among couples questioned in 1988, but perhaps even more so, of their struggle against resigning themselves to remaining childless; there is, thus no real evidence to suggest that there has been a true increase in sub-fecundity or sterility. /// La proporción de mujeres de 25 a 44 años que declaran haber tenido dificultades para concebir, ha progresado fuertemente entre 1978 y 1988, pasando de 18 a 30 por ciento. Medianamente, ellas esperaron menos de dos años para llegar al embarazo y este retardo no parece haber cambiado entre una fecha y la otra. Si se excluyen los tiempos de retardo inferiores o iguales a 12 meses, la proporción de mujeres "subfertiles" disminuye de 30 a 17 por ciento (en 1988), lo que constituye todavía un porcentage elevado y probablemente muy próximo al de las parejas que consultan un médico por "esterilidad" por lo menos una vez en su vida. La proporción más fuerte de dificultades declaradas en 1988, en relación a 1978, podría resultar de una gran impaciencia en las parejas interrogadas en 1988 y sobre todo de una menor resignación de éstas en relación a las interrogadas en 1978; entonces no es seguro que haya habido una real progresión de la subfertilidad o de la esterilidad.
The Center for Population Research collected 30,655 recorded menstrual cycles from 2,316 women. Ninety-five percent of all cycles were between 15 and 45 days long. The mean and standard deviations for the total number of cycles were 29.1 and 7.46, respectively. Cycle lengths between 15 and 45 days averaged 28.1 days with a standard deviation of 3.95 days. Variability of menstrual-cycle lengths is highest for women under 25 years of age and declines steadily to reach a minimum for ages 35 to 39. It is then followed by a slight increase for women aged 40 to 44. The pattern of variability by age is demonstrated equally well by the percent of cycles between 25 and 31 days in length as by the standard deviation.
Professeur à V Université de Rome, Rome, Italie. J'appelle fécondabilité de la femme la probabilité que la femme mariée soit fécondée dans le mois, abstraction faite de toute pratique malthusienne ou néo-malthusienne destinée à limiter la procréation. Il est inutile d'insister sur l'importance théorique et pratique qu'aurait la mesure de la fécondabilité. Nous aurions en particulier le moyen de décider quelle partie des différences que l'on observe entre les coefficients de natalité de différents pays, de différentes classes sociales, de différentes époques provient de causes physiologiques et quelle partie provient de causes volontaires. Il est inutile aussi de s'arrêter à démontrer que l'on ne peut pas mesurer directement la fécondabilité. On comprend aisément en effet que l'on n'est pas en état de mesurer les conséquences des pratiques malthusiennes et néo-malthusiennes sur la natalité. Nous ne connaissons pas d'ailleurs la fréquence des avortements ovulaires qui ont lieu dans les premiers mois de la grossesse. On peut, au contraire, songer à une mesure indirecte de la fécondabilité, basée sur les considérations qui suivent.
Objective To investigate lifetime prevalence of infertility, the seeking of infertility treatment and outcomes of treatment.Design Cross-sectional postal questionnaire study.Setting County of Copenhagen, Denmark.Subjects Three thousand, seven hundred and forty-three women, 15 to 44 years old, selected at random were asked about infertility, their seeking of infertility treatment, diagnoses provided by their doctors and subsequent parenthood. Response rate was 78%, n= 2865. A random sample of non-responders was interviewed by telephone.Main outcome measures Fertility status, seeking of infertility treatment, subsequent deliveries and adoptions.Results Of the women who had attempted to have a child, 26.2% had experienced infertility; 4.1% of the women aged 25 to 44 years were currently primarily infertile and 8.6% had involuntarily not delivered a first child; 47.4% of the infertile women had sought infertility treatment. Significant predictors for seeking infertility treatment were school education > 9 years and not having delivered a child. Of the infertile women 54.9% subsequently had a child. Only 30% of these reported that the successful delivery was treatment-related.Conclusions The health care system should see to it that infertile couples from lower social classes are offered information on the possibility of infertility treatment. High quality infertility treatment has to include both the “supply” of taking care of the infertile couple's psychosocial strain and the goal of ensuring successful pregnancies.
Inseminations were carried out according to a protocol which recommended, during the first two menstrual cycles, a single intracervical insemination, using one dose of semen and no accompanying therapy. For 821 such cycles, the success rate per cycle was 12%. Cycle days were numbered with respect to the last day of hypothermia, and the highest success rates were obtained on days -1 (21%) and -3 (20%). Three other factors were studied: dilation of the cervix, abundance of cervical mucus, and spinnbarkheit. For these factors, conception rates were 14% when the cervix was dilated (versus 8%, P<0.05), 15% when there was abundant mucus (versus 6%, P<0.001), and 18% when spinnbarkheit was ≥ 10 cm (versus 9%, P<0.001). Combinations of these factors are considered.
To investigate whether semen quality has changed during the past 50 years.
Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991).
14,947 men included in a total of 61 papers published between 1938 and 1991.
Mean sperm density and mean seminal volume.
Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density.
There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.
To estimate the prevalence and main causes of infertility, a multicentre survey was conducted over 1 year (July 1988-June 1989) in three regions of France. All the 1686 couples in these regions, who consulted a practitioner for primary or secondary infertility during this period, were included in the investigation. The prevalence rate of infertility was found to be 14.1%, indicating that one woman out of seven in France will consult a doctor for an infertility problem during her reproductive life. The main causes of female infertility were ovulation disorders (32%) and tubal damage (26%), and of male infertility oligo-terato-asthenozoospermia (21%), asthenozoospermia (17%), teratozoospermia (10%) and azoospermia (9%). Infertility was also found to be caused by disorders in both the male and female partners together; thus in 39% of cases both the man and woman presented with disorders. The woman alone was responsible for infertility in one-third of cases and the man alone in one-fifth. Unexplained infertility was found in 8% of the couples surveyed.
An analysis of the influence of women's age on the results of in-vitro fertilization was performed, using 5590 attempts collected during the year 1986. Increasing age was found to be related to decreased success rates from 19.8% per attempt below the age of 25 years, to 9% per attempt at 40 years or more. A cut-off point was found between the ages of 36 and 37 years, using a mathematical model. The decrease was related to a reduction in oocyte production (4.3 +/- 2.8 at 25 years or less and 3.3 +/- 2.1 at 40 years or more, P less than 0.001), and to a reduced implantation rate, whatever the number of transferred embryos. These findings were not due to spouse's age, rank of attempt, infertility diagnosis or oocyte stimulation regimen, since the effect of age remained significant when a logistical model including these confounders was applied. Finally, a woman's age must be considered as a prognostic factor when IVF is proposed to infertile couples.
Ovulation induction with various hormonal agents has become a standard component of in vitro fertilization (IVF) cycles to obtain multiple oocytes. Failure to anticipate the retrieval of more than two oocytes often results in cancellation of the cycle. In this study, we report our results in 80 unstimulated IVF cycles. Serum estradiol (E2) and pelvic ultra-sound monitoring were begun on day 9 of the cycle. Human chorionic gonadotropin (hCG) was administered when the E2 level exceeded 180 pg/mL and the dominant follicle was greater than 18 mm. Eighteen pregnancies were obtained (22.5%/cycle), and 14 (17.5%/cycle) are ongoing. We conclude that favorable results can be obtained from unstimulated IVF cycles, despite replacement of a single embryo.
A prospective study of fertility was conducted from 1977 to 1982. Analysis of the relation between cigarette smoking and occurrence
of a pregnancy was performed on 1887 couples. The actuarial pregnancy rate was 82.9% at the end of a year. Cigarette smoking
by both members of the couple was found to be related to decreased fertility when this factorwas considered alone. But after
including all the confounding covariates in a Cox semi-proportional hazards model for survival data, no relationship remained
between cigarette smoking and fertility. Odds ratios were respectively 0.86 (95% confidence interval: 0.63, 1.19) and 0.99
(0.85, 1.14) for women smoking and men smoking. This could suggest that the relationship found by other authors might be at
least partly explained by a relation between cigarette smoking and other factors related to fertility.
National estimates of demographic characteristics are shown for infertile women compared with those who were fecund, women with primary versus secondary infertility, and infertile women who had, and had not, sought infertility services. Overall, 30% of infertile women had primary infertility, and 70% had secondary infertility. Women with primary infertility were twice as likely to seek services as women with secondary infertility. Many demographic characteristics of women with secondary infertility who sought services differed from those of women who had not sought services. There were fewer differences among women with primary infertility. These findings have implications for the generalizability of results from clinic-based studies and suggest that more research is needed on the barriers to service among infertile couples.
The following factors may all have contributed to the apparent increasing concern with infertility services: the number of infertile couples in the population, the proportion of infertile couples seeking infertility services, the number of physicians with an interest in infertility services, and the contemporary social milieu. Based on a consideration of major demographic, social, and economic factors, we predict that the demand for infertility services will not decrease during the next decade. Only major improvements in prevention can substantially reduce the human suffering caused by infertility. We believe the most important intervention in the near future will probably be in preventing infertility of infectious etiology - in other words, sexually transmitted infertility.
The percentage of steriles and the fecundability of non-steriles among a given population can be estimated by a probabilistic model from observations made on delays to first conception. The maximum likelihood method of estimation that was used takes into account all available information, though some of these observations may be incomplete due to a variable follow-up amongst the couples. The model is illustrated with data provided by a prospective study.
Couples consulting for infertility are a highly select group, and this makes the evaluation of the effectiveness of a type of therapy difficult. The most obvious selection results from the time they have been unsuccessfully waiting for a conception. Because fecundability is variable from one couple to another, the monthly probability of conceiving after 2 or 3 years of waiting time is low, but the proportion of couples who will conceive within 1 year is still significant and can be predicted. However, in most cases, couples submitted to a specific treatment include hypofertile and totally sterile couples, in unknown proportion. This fact makes difficult the measurement of the effectiveness of therapy, and procedures including control groups should be used. An example of such a process is given.
The relationship between age and semen characteristics has been studied; any effect due to the influence of the length of abstinence preceding ejaculation was eliminated. There is an improvement in semen characteristics up to 25 years of age, followed by a leveling off and a subsequent decrease. This variation is not significant as far as the sperm count, semen volume, and the total number of spermatozoa are concerned. The variation, although small, is highly significant for the morphologic characteristics and prefreeze and postthaw motility. The values for the older subjects were significantly lower for postthaw motility in the group 36 to 40 years of age, in the group 41 to 45 years of age for morphologic normality, and in the group 46 to 50 years of age for prefreeze motility. The lower values in the group 21 to 25 years of age are particularly noticeable with regard to morphologic characteristics. The same curve is encountered in the variation with age of each abnormal form, but the most marked variation is found in the increased percentage of coiled tails, which first appears in the group 36 to 40 years of age.
Pelvic inflammatory disease is used herein synonymously with acute salpingitis. In modern industrialized countries, the annual incidence of PID in women 15 to 39 years of age seems to be 10 to 13 per 1,000 women, with a peak incidence of about 20 per 1,000 women in the age group 20 to 24 years. Since 1960 an increase in incidence by a factor of 1.6 to 1.9 has been observed in the age group 20 to 29 years. The incidence of PID is correlated strongly with the prevalence of sexually transmitted diseases, although a fraction of the infections might be of endogenous origin. Use of intrauterine contraceptive devices and operations for legal abortions contribute to the increase in incidence. The prevalence of women in the post-PID state has increased by a factor of about 1.5 since 1960. Women in the post-PID state have a tenfold increased risk for ectopic pregnancy and 25% of the increase in ectopic pregnancy can be accounted for by the increase in post-PID women. Infertility after PID ranges between 5.8% and 60% depending on severity of infection, number of infections, and age of the women. The fraction of women rendered infertile because of PID has increased by a factor of about 1.6 since 1960.
The decrease in the fecundity of women who have passed a certain age is generally acknowledged but supporting data on natural reproduction are scarce. Artificial insemination with donor semen (AID) seems to present an opportunity to control certain variables in the study of female fecundity over time, but the few studies published to date have been carried out in small populations. We studied 2193 women who were receiving AID and whose husbands were totally sterile. The curve of the cumulative success rate for the women 25 years of age or younger was similar to that for women 26 to 30 years old. However, this curve showed a significant decrease in the cumulative success rate for women 31 to 35 years of age. This decrease was even greater for those over 35. Similar decreases with age were observed for the mean conception rate per cycle. Our data therefore provide evidence of reduced fecundity with age, which begins at some point after the age of 30 years.
Measurements of human chorionic gonadotropin (hCG) have been used to assess early embryo loss in women. Urine samples obtained from a control group of sterilized women with normal ovulatory menstrual cycles enabled a concentration limit of 56 IU/l to be determined so that any nontrophoblastic hCG or other cross-reacting compounds could be accounted for. One hundred ninety-eight ovulatory cycles were collected from a normal population attempting to conceive. Fecundability was 22% to 27% for this population. The risk of pregnancy in exposed ovulatory cycles was 59.6%; however, 61.9% of conceptuses will be lost prior to 12 weeks. Most of these losses (91.7%) occur subclinically, without the knowledge of the mother.
The incidence of disorders of development of the male reproductive tract has more than doubled in the past 30-50 years while sperm counts have declined by about half. Similar abnormalities occur in the sons of women exposed to diethylstilbestrol (DES) during pregnancy and can be induced in animals by brief exposure to exogenous oestrogen/DES during pregnancy. We argue that the increasing incidence of reproductive abnormalities in the human male may be related to increased oestrogen exposure in utero, and identify mechanisms by which this exposure could occur.
The objective was to investigate lifetime prevalence of infertility, the seeking of infertility treatment and outcomes of treatment. A random sample of 3,743 women, 15 to 44 years old, were asked about infertility, their seeking of infertility treatment, diagnosis provided by their doctors and subsequent parenthood in a postal questionnaire. Response rate was 78%. Of the women who had attempted to have a child, 26.2% had experienced infertility; 4.1% af the women aged 25 to 44 years were currently primary infertile and 8.6% had involuntarily never delivered a child; 47.4% of the infertile women had sought infertility treatment. Significant predictors for seeking treatment were over nine years of school education and not having delivered a child. Of the treated infertile women 54.9% subsequently had a child. Only 30% of these reported that the successful delivery was treatment-related. The health care system should ensure that infertile couples from lower social classes are offered information on the possibility of infertility treatment.
Semen analysis is part of the routine assessment of infertile couples. WHO defines a sperm concentration above 20x10(6) per mL seminal fluid as normal. We studied the association between semen quality and the probability of conception in a single menstrual cycle in Danish couples with no previous reproductive experience.
In 1992-94, we invited 52,255 trades-union members aged 20-35 years, who lived with a partner and had no children to take part in the study; 430 couples agreed. The couples discontinued use of contraception, and were followed up for six menstrual cycles or until a pregnancy was verified within this period. Each man was asked to provide a semen sample at enrolment (which was analysed without freezing). Women kept a daily record of vaginal bleeding and sexual activity. The association between semen quality and likelihood of pregnancy was assessed by logistic regression, adjusted for sexual activity and female factors associated with low fertility.
There were 256 (59.5%) pregnancies among the 430 couples: 165 (65.0%) among those with a sperm concentration of 40x10(6)/mL or more and 84 (51.2%) among those with lower sperm concentrations. The probability of conception increased with increasing sperm concentration up to 40x10(6)/mL, but any higher sperm density was not associated with additional likelihood of pregnancy. The proportion of sperm with normal morphology was strongly related to likelihood of pregnancy independently of sperm concentration. Semen volume and motility were of limited value in pregnancy prediction.
Our study suggests that the current WHO guidelines for normal semen quality should be used with caution. Some men with sperm counts above the lower limit of the normal range defined by WHO may in fact be subfertile.
To estimate the effects of aging on the percentage of outwardly healthy couples who are sterile (completely unable to conceive without assisted reproduction) or infertile (unable to conceive within a year of unprotected intercourse).
A prospective fecundability study was conducted in a sample of 782 couples recruited from 7 European centers for natural family planning. Women aged 18-40 years were eligible. Daily intercourse records were used to adjust for timing and frequency of intercourse when estimating the per-menstrual-cycle probability of conception. The number of menstrual cycles required to conceive a clinical pregnancy and the probability of sterility and infertility were derived from the estimated fecundability distributions for men and women of different ages.
Sterility was estimated at about 1%; this percent did not change with age. The percentage infertility was estimated at 8% for women aged 19-26 years, 13-14% for women aged 27-34 years and 18% for women aged 35-39 years. Starting in the late 30s, male age was an important factor, with the percentage failing to conceive within 12 cycles increasing from an estimated 18-28% between ages 35 and 40 years. The estimated percentage of infertile couples that would be able to conceive after an additional 12 cycles of trying varied from 43-63% depending on age.
Increased infertility in older couples is attributable primarily to declines in fertility rates rather than to absolute sterility. Many infertile couples will conceive if they try for an additional year.
To evaluate the association patterns and quantify the effects of lifestyle on time to pregnancy (TTP).
Observational study.
Teaching hospitals in Hull, United Kingdom.
Two thousand and one hundred twelve consecutive pregnant women.
A questionnaire inquiring about TTP, contraceptive use, pregnancy planning, previous subfertility/pregnancies, age, and lifestyle characteristics of either partner.
We compared TTP, conception rates, and relative risk of subfecundity between subgroups with different lifestyle characteristics.
We found that TTP was significantly longer if the woman or partner smoked >15 cigarettes/day (P<.001 and.04, respectively), the partner consumed >20 alcohol units/week (P<.001), the woman's body mass index was >25 kg/m(2) (P<.001), their coffee and/or tea intake was >6 cups/day (P=.04), or if they were socially deprived (P<.001). Each of these effects remained unchanged after adjusting for the potential confounders. The relative-risks of subfecundity with each of these variables ranged between 1.4 to 1.9 (1.4 to 3.6 after adjustment). The effects of coital frequency and recreational drug use were insignificant. Couples who had >4 negative lifestyle variables had a sevenfold longer TTP; their conception probabilities fell by 60%, and they were 7.3-fold more likely to be subfecund than those without negative variables.
Lifestyle has a significant and cumulative impact on fecundity. Dose-dependent effects occur with smoking, alcohol, and tea/coffee consumption. Appropriate counseling could result in substantial reductions in the referrals for fertility investigations and treatments.
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.
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).
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.
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 International Committee Monitoring Assisted Reproductive Technologies (ICMART) is an independent international nonprofit organization that has taken a leading role in the development, collection, and dissemination of worldwide data on assisted reproductive technology (ART). Information on availability, efficacy, and safety is provided to health professionals, health authorities, and the public. The glossary facilitates dissemination of ART data through a set of agreed-upon definitions, as seen in the most recent World Report on ART. It provides a conceptual framework for further international terminology and data development of ART.
Several studies have examined the effect of in utero exposure to smoking and fecundity among the offspring but the findings are contradictory. We therefore studied the waiting time to first pregnancy (TTP) and exposure to smoking in utero and childhood among Danish twins born between 1931 and 1952. Information about TTP, exposure to mothers smoking in pregnancy, exposure to smoking in childhood and current smoking among the male twins and smoking in their own pregnancy among female twins was collected by interview. Fecundability odds ratio (FOR) estimating the odds of conception in a cycle among exposed compared to the unexposed were calculated separately for female and male twins. A total of 1653 female and 1598 male twins reported a TTP. Female twins, exposed in utero, had reduced fecundability after control for confounders (FOR = 0.81; 95% CI 0.67-0.99). A nonsignificant increase in fecundity among male twins exposed to smoking in utero was found (FOR = 1.12; 95% CI 0.89-1.40). Among dizygotic twins of opposite sex sharing the same in utero exposures, the future fecundity of the male twin was unaffected by in utero exposure (FOR = 0.97; 95% CI 0.60-1.55) whereas the female twin had reduced fecundity (FOR = 0.65; 95% CI 0.47-0.91). This study supports that smoking is hazardous to the female fetus not only in the short term but also affects her future ability to conceive and makes it even more important to advise pregnant women to stop smoking.
INTRODUCTION
The purpose of the present study was to review existing population surveys on the prevalence of infertility and proportion of couples seeking medical help for fertility problems.
METHODS
Population surveys, reporting the prevalence of infertility and proportion of couples seeking help in more and less developed countries, were reviewed.
RESULTS
Estimates on the prevalence of infertility came from 25 population surveys sampling 172 413 women. The 12-month prevalence rate ranged from 3.5% to 16.7% in more developed nations and from 6.9% to 9.3% in less-developed nations, with an estimated overall median prevalence of 9%. In 17 studies sampling 6410 women, the proportion of couples seeking medial care was, on average, 56.1% (range 42–76.3%) in more developed countries and 51.2% (range 27–74.1%) in less developed countries. The proportion of people actually receiving care was substantially less, 22.4%. Based on these estimates and on the current world population, 72.4 million women are currently infertile; of these, 40.5 million are currently seeking infertility medical care.
CONCLUSIONS
The current evidence indicates a 9% prevalence of infertility (of 12 months) with 56% of couples seeking medical care. These estimates are lower than those typically cited and are remarkably similar between more and less developed countries.
Reproductive disorders of newborn (cryptorchidism, hypospadias) and young adult males (low sperm counts, testicular germ cell cancer) are common and/or increasing in incidence. It has been hypothesized that these disorders may comprise a testicular dysgenesis syndrome (TDS) with a common origin in fetal life. This has been supported by findings in an animal model of TDS involving fetal exposure to n(dibutyl) phthalate, as well as by new clinical studies. Recent advances in understanding from such studies have led to refinement of the TDS hypothesis, highlighting the central role that deficient androgen production/action during fetal testis development, may play in the origin of downstream disorders.
Fertility rates and aging. In: Ageing, reproduction and the climacteric
- J Menken
- U Larsen
The overall problem in man Comparative aspects of reproduction failure
- At Hertig