Delaying Chldbearing

PAPERS Delaying childbearing: effect o f a g e on fecundity a nd outcome o f pregnancy Boukje M va n Noord-Zaadstra, Caspar W N Looman, Hans Alsbach, J D i k F Habbema, Egbert R te Velde, J a n Karbaat Toeqepast Natuurwetenschapp4 Onderzoek Institute ( Preventive Health C a Child Health Divisio P O B ox 124, 2300 AC Leiden, T he Netherlands Boukje M v a n Noord Zaadstra, Msc, epiden Department o f Publi Health and Social Medicine, Erasmus University Medical S Rotterdam, T h e Netherlands Caspar W N Looman statistician J D ik F Habbema, P H professor o f medical d e c sctences Department o f Obst a n d Gynaecology, University Hospital, Utrecht, T h e Nether Hans Alsbach, Msc, medical data manager Egbert R te Velde, M I professor o f reproductiv medicine Cryo Biological Laboratories,Bijdor Barendrecht, T h e Netherlands J an Karbaat, M D , m ed director Correspondence t o : M r s v a n Noord-Zaad, B M J 1991;302:1361-5 Abstract Objectives-To study t h e a g e o f the start o f t h e fall (critical age) i n fecundity; the probability o f a pregnancy leading t o a healthy baby taking into account t h e a g e o f t h e woman; and, combining these results, to determine t h e a g e dependent probability o f getting a healthy baby. Design-Cohort study of a l l women w ho h a d entered a donor insemination programme. Setting-Two fertility clinics serving a large part o f Th e Netherlands. Subjects-Of 1637 women attending f o r artificial insemination 7 1 fulfilled the selection criteria, being married t o a n azoospermic husband an d nulliparous a n d never having received donor insemination before. Main outcome measures-The number of cycles before pregnancy ( a positive pregnancy test result) elijk or stopping treatment; a n d result o f t h e pregnancy o f (successful outcome). are, Results-Of t h e 75 1 women, 55 5 became pregnant a n d 4 6 1 ha d healthy babies. T he fall i n fecundity w as estimated t o start at around 3 1 years (critical age); after 12 cycles the probability o f pregnancy i n a woman aged > 3 1 w as 0-54 compared with 0-74 i n a tiologist woman aged 20-31. After 2 4 cycles this difference ha d decreased (probability o f conception 0-75 i n c women > 3 1 a n d 0-85 i n women 20-31). Th e probability o f having a healthy baby also decreased-by 3-5% a year after t h e a g e of 3 0 . Combining both these chool, a g e effects, t h e chance o f a woman aged 3 5 having a healthy baby w a s about halfthat o f a woman aged 2 5 . MSC, Conclusion-After the a g e o f 3 1 the probability o f MSC, conception fails rapidly, b u t this c a n b e partly [ D , compensated f or b y continuing insemination f o r cision more cycles. I n addition, t h e probability of an adverse pregnancy outcome starts t o increase a t about the same age. etrics Introduction rlands Female fecundity (the ability t o conceive) i s gener- ally acknowledged t o decrease with increasing age, bu t D , t h e beginning o f t he fall i n fecundity ha s n o t been )e pinpointed t o a specific age. Such information i s o f importance t o t h e increasing number o f women w h o a r e delaying childbearing. I n naturally selected popu- lations studying t h e decrease i n fecundity caused b y biological factors i s confounded b y diminished sexual activity with ag e a n d possibly also b y a decrease i n male lical fertility. Schwartz a n d Mayaux studied t h e a g e effect i n women treated b y artificial donor insemination. Their data suggest that reduced fecundity starts around t h e a ge range 31-35, but their follow u p time o f 1 2 cycles stra. w a s relatively short. Older women w h o continue treatment f o r a much longer period ma y eventually conceive.2 Moreover there i s evidence that advancing maternal a g e h a s an adverse effect o n t h e outcome o f pregnancy because o f a higher abortion a n d perinatal mortality.3 O u r study o f a cohort of women receiving donor insemination wa s undertaken t o examine t h e age o f t h e start o f th e fall i n fecundity (critical age), t h e probability o f a pregnancy leading t o a healthy baby taking into account th e a g e o f the woman, a n d t he ag e dependent probability o f getting a healthy baby, b y combining t h e critical a g e a nd t h e probability o f a pregnancy leading t o a healthy baby. Subjects a n d methods T w o fertility clinics (A and B) serving different geographic areas participated i n t h e study. Women were referred t o t h e clinics b y a general practitioner o r a specialist. T h e source population consisted o f a l l women w h o attended the clinics f o r artificial donor insemination between January 1973 a n d t h e years when t h e protocols were changed from treatment with fresh semen t o frozen semen (1980 f o r clinic A a n d 1986 f o r clinic B ) . A total of 1637 women entered the artificial insemination programme i n t he t w o clinics, 1036 i n clinic A a n d 6 0 1 i n clinic B W e studied t h e 7 5 1 women, 4 4 4 from clinic A a n d 2 39 from clinic B , w h o satisfied th e selection criteria-that i s, women w h o were married t o an azoospermic husband, were nulliparous, a n d h a d never received artificial insemination before. Insemination procedures were usually conducted i n every subsequent menstrual cycle. Women were inseminated intracervically, a n d timing o f insemination w a s estimated o n t he basis o f t h e basal body temperature chart a n d b y judging the quality o f cervical mucus. On average the number o f tions per cycle w a s three f o r clinic A a n d t w o f o r clinic B . Fresh semen w a s used from donors aged 25-45 with a proved fertility (having fathered a t least o ne child) a n d with sperm properties satisfying t h e World Health Organisation criteria. I n clinic A t he specialists were free t o prescribe sup- plementary treatment such a s induction of ovulation b y clomiphene i f a woman d i d not conceive aftera f e w cycles. In clinic B induction of ovulation w a s largely confined t o women w ho proved t o have anovulatory cycles o r w h o h a d very long cycles during a n obser- vation period before treatment. I f induction of ovulation w a s started the treatment w a s continued i n subsequent insemination cycles. I f a woman di d n o t conceive hysterosalpingography wa s performed after t h e sixth cycle a n d laparoscopy after t h e twelfth cycle. A l l women were followed until t h e e n d o f treatment with artificial insemination. T he e n d w a s defined a s t h e result o f each woman's last insemination cycle, being either a confirmed pregnancy (success) o r stopping treatment without pregnancy (failure). Only first con- B M J VOLUME 302 8 JUNE 1991 1361

Delaying Chldbearing

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