Problems of multiple births after ART: medical, psychological, social and financial aspects

In recent years, a growing number of infants born to migrant mothers following the use of assisted reproductive technologies (ART) have been admitted to our neonatal intensive care unit, usually due to problems resulting from multiple birth and prematurity. Higher order multiple births have become more frequent due to increased use of ovulation-inducing drugs and reproductive techniques. Whereas in 1993 an estimated total of 30 000 babies were born worldwide after assisted conception (Lancaster, 1996), the most recent report on ART indicates that for the year 1995, 16 520 babies were born by means of ART in the USA and in Canada alone (SART/ASRM, 1998). Spontaneous rates were 1.05–1.35% for twins and 0.01–0.017% for triplets (Guttmacher, 1953), but the actual rate of multiples was 3.0%. Of 796 013 liveborn infants registered in Germany in 1996, 22 126 were twins, 1004 were triplets and 64 were quadruplets (Statistisches Bundesamt Wiesbaden, 1998). The incidence of multiple gestation pregnancies was 5–13% with clomiphene citrate (Scialli, 1986; Levene, 1991), 10–15% with gonadotrophins, 15–20% with gonadotrophins combined with intrauterine insemination (IUI) (Martin et al., 1993), 19–38% with intra-Fallopian gamete transfer (GIFT) (Craft et al., 1988; MRC working party, 1990; SART/ASRM, 1998), 16–66% with intracytoplasmatic sperm injection (ICSI) (Bonduelle et al., 1996, Slotnick and Ortega, 1996, Wennerholm et al., 1996, SART/ASRM, 1998), and 15–36% with in-vitro fertilization (IVF) (MRC working party, 1990; Rein et al., 1990; Bollen et al., 1991; SART/ASRM, 1998). Many countries had IVF multiple birth rates of >20% in 1993 (Lancaster, 1996), with rates up to 37% occurring in the USA and Canada in 1995 (SART/ASRM, 1998). The proportion of transfer cycles in which more than three embryos were transferred has varied from none in Germany and the UK to 51% in Latin America and 49% in Israel (Lancaster, 1996). In Berlin, 30.4% of all couples treated for infertility come from abroad (Yüksel et al., 1996). Frequently, couples are Turkish migrants from the countryside whose patriarchal societies follow the Islamic tradition. They believe the purpose of marriage is to generate numerous and male descendants, and a couple's social position is measured by the number of children with whom they are blessed. In Berlin, many Turkish couples live in a ghetto situation without the necessity of learning the German language. They are unskilled workers in a low economic class. Infertile Turkish couples seek medical treatment much earlier because their social surroundings intensify the individual problem of childlessness. Due to their problems with the language, the couples have difficulty in comprehending modern medical reproductive procedures, nor are they likely to receive information and consultation in their native language. We believe that in migrant mothers wishing for assisted reproduction, uncritical treatment is not uncommon. The aim of the present article is to discuss medical, psychological, social, and financial aspects of infertility treatment across and within different cultural backgrounds, and to emphasize the need for a change in current treatment regimes and for appropriate counselling. A prospective longitudinal cohort study was performed in 96 very low birth weight and 192 term infants born between July 1992 and December 1993 in the Charité Virchow-Hospital, Berlin, Germany. The design of the study and the psychomotor development of these infants have been described previously (Heiser et al., 1995). The follow-up included a structured interview, which allowed the estimation of frequency of ART in the population. In the study group, 24 of the infants were born after ART (ovulation-inducing drugs, n = 11; IVF/IUI, n = 13). Seven of the 17 mothers had already given birth to at least one infant. Nine (37.5%) of the infants born after infertility treatment were of Turkish origin which accounts for only 10% of the total population. The median age was 27.4 years for Turkish women undergoing assisted reproduction and 30.6 years for German women. None of the five Turkish mothers of the nine infants had obtained an educational degree or had acquired any professional skill. One of the 12 mothers (11 German and one American) of the remaining children had no educational degree and six women had no professional skill. There were no differences between the German and Turkish families concerning housing (71 versus 68.6 m2), number of rooms (2.6 versus 2.4), and net monthly income. The case reports were derived from neonatal charts, maternal interview, results of follow-up examinations, and information obtained from the gynaecologist and the family's paediatrician. The parents are Turkish migrants of Islamic religion, are first degree cousins, and have been married for 9 years. The mother has lived in Germany since 1978, but does not speak German fluently. The father migrated to Germany in 1987 and cannot speak German. Both parents had 5 years of school education. The mother was 30 year old gravida I para I, the cause of infertility was high androgenization. After stimulation with follicle stimulating hormone (FSH) and luteinizing hormone (LH), a healthy baby (birthweight: 4390 g) was born. After 11 months the mother wished for another child. The family was living in a one-room apartment in Berlin. She was then treated a second time with FSH and LH which resulted in a quintuplet pregnancy. One was a missed abortion in early pregnancy. After 5 weeks vacation in Turkey she was admitted at 24 weeks and 5 days gestation with haemorrhage and contractions, 4 days after membrane rupture. Despite i.v. Cefotiam and Fenoterol, contractions and signs of infection persisted, and a Caesarean section was performed at 25 weeks. The infants had multiple medical problems, some of which are detailed in Table I, and were discharged with varying degrees of cerebral palsy. The hospital cost for the total of 714 intensive and special care days was US$579 702, the cost for additional 912 hospital days during the children's' first 4 years of life was US$111 070. Continuing care for the severely handicapped children will be >US$1 million. The father (who works as a baker) has unfavourable working hours, leaves all care and education of the five children to the mother, who permanently feels overburdened and suicidal. The children are frequently left to themselves. As a result, they were not sufficiently stimulated emotionally and intellectually, which has led to emotional and social deprivation. The parents are students from Southeast Asia and have lived in Germany for 3.5 years. They are Protestants, married, and live in a three-room apartment and have difficulties with the German language. The mother is a 32 year old gravida IV, para I, three abortions occurred in early pregnancy. IVF resulted in a triplet pregnancy which was selectively reduced to twins at 13 weeks gestation. At 14 weeks gestation, cerclage and tocolysis were performed because of contractions. Haemorrhages occurred at 3, 4, and 5 months gestation, and membranes ruptured at 28 weeks and 4 days. Lung maturity induction was attempted with β-methasone, but the infants had to be delivered by Caesarean section 2 h later. The first born twin girl had a birthweight of 1215 g, length 34 cm, head circumference 26.5 cm, umbilical artery pH 7.25, Apgar score (1'/5′) 4/8, CRIB (clinical risk index for babies) score 4. She was intubated when only 6 min old, received surfactant for grade III respiratory distress syndrome, was extubated after 10 h, and received 14 days of nasal continuous positive airway pressure (CPAP). Cranial sonography revealed no intracranial haemorrhage, fundoscopy showed grade I retinopathy of prematurity which resolved up to day 52, when the twins were discharged. Follow-up at 7 months corrected age performed at their home showed a slight asymmetry, normal developmental age and Griffiths developmental quotient of 111. The second born twin was a boy, birthweight 1060 g, length 34.5 cm, head circumference 25.7 cm, umbilical artery pH 7.25, Apgar score (1'/5′) 7/8, CRIB score 2. He was intubated for grade III respiratory distress syndrome (RDS), received surfactant, and was extubated 11 h later. He was reintubated on day 12 because of septicaemia, antibiotic treatment followed for 10 days. After 18 days of ventilation, extubation was followed by 7 days of nasal CPAP. Cranial ultrasound showed no haemorrhage, grade I retinopathy resolved up to the time of discharge; brain stem auditory evoked potentials revealed elevated hearing threshold (70 dB nHL). Follow-up at 7 months showed normal development and Griffiths developmental quotient was 111. Immediate postnatal hospitalization cost for 138 days in both twins was US$116 646. The mother is a 15-year old unmarried Islamic gravida I, para I from Africa. She speaks no German and only some words in English. She had attended school for 6 years, but did not acquire any professional skill. Medication with human chorionic gonadotrophin (HCG) was given in Africa to treat allegedly irregular cycle and resulted in triplet gestation. Cervical canal was closed operatively at 20 weeks. Due to social pressures and religious conflicts the young woman came to Germany at 26 weeks gestation and was given tocolysis for premature contractions and β-methasone in an attempt to accelerate lung maturation. After 32 weeks 1 day, a Caesarean section was performed because of pre-eclampsia. Intra- and post-operatively, she developed acute pulmonary oedema with left ventricular failure (ejection fraction <15%), was resuscitated in the operation room, and required assisted ventilation for 9 days. She was discharged after 34 days and readmitted to the intensive care unit of another hospital 13 days later for a further 12 days of treatment. The first born boy (1200 g, umbilical arterial pH 7.21, Apgar score (1'/5′) 4/7, CRIB score 1) and the second born boy (1290 g, umbilical arterial pH 7.24, Apgar score (1'/5′) 7/5, CRIB score 1) had no respiratory problems, the third born girl (1230 g, umbilical arterial pH 7.21, Apgar score (1'/5′) 5/6, CRIB score 1) had respiratory failure due to fluid on the lung, required ventilation for 7 h and nasal CPAP for 4 days. All three infants were discharged to a foster-home on day 40 after uneventful parenteral and enteral feeding and satisfactory growth. At follow-up at term, the infants were well. They were looked after exclusively by the nurses of the Mother-Children-Home, which has organized a special care service for triplets. Due to the heart insufficiency, the mother is unable to care for her children; a peripartal cardiomyopathy is assumed which has a high risk of recurrence and is a contraindication for further pregnancies. She does not understand German and has no residence permit, no income, and no medical insurance. The family of the young mother is undermining contact with the children's father. Taking into consideration her religious and cultural background, the prospects for this unmarried, chronically ill 15-year old mother with three children would be even more dismal if she returns to Africa. The mother is a 24-year old Turkish woman living in Germany since her birth, had 9 years of school education, is unemployed and lives on social welfare. She speaks German fluently. At the age of 18 years she was married to a Turkish man. During the marriage, three pregnancies were legally aborted. After 4 years, she was divorced. After 1 year she became pregnant by her new Turkish partner, with whom she did not live. Ovulation was induced with clomifene citrate without his knowledge (according to her), in an attempt to motivate him to live with her. The pregnancy was uneventful up to 25 weeks 6 days gestation when the mother was admitted with labour and dilated cervix. As the contractions could not be stopped, the triplets were born by Caesarean section 1 h after admission. The infants had multiple medical problems which are detailed in Table II. Our cases (which are not unique) show how the immediate granting of a wish for a child may involve unforeseeable consequences. The recommendations of the World Health Organization (WHO) define the unfulfilled wish for children after 2 years infertility as a disease in need of treatment (Leidenberger, 1989). German health insurance companies cover assisted reproduction if: (i) the procedure is indicated by an expert physician and success of pregnancy is likely; (ii) the couple is married and the spermatozoon is from the husband and the egg is from the wife; (iii) pre-treatment counselling is given by a physician, who himself does not perform the treatment, and (iv) the parents are referred to a specialized physician or centre licensed for assisted reproduction. Worldwide, 8–17% of all married couples are infertile (Callahan et al., 1994; Glander, 1996). The diagnosis of infertility represents a critical life event followed by suffering, loss of self-esteem, and depression. However, the intensity of the desire for a child does not guarantee adequate developmental conditions for the children. Motives often include the hope that children may improve the marital situation or solve personal problems, remove boredom and loneliness, and give a meaning to their parents' life. Assisted reproduction is associated with an increased rate of high order pregnancies, although this has recently decreased (Rjosk et al., 1995). Multiple pregnancies always represent an increased risk for mother and children. The mean gestational age at which triplets and quadruplets were delivered was 34–35 weeks, but there are still many immature infants prone to high morbidity and mortality (Levene, 1991). Due to prematurity and low birthweight, mortality and morbidity are markedly higher in triplets than in singletons. Postnatal problems result from multiple birth (29%) and prematurity (23%) and include: RDS, persistent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), septicaemia, intraventricular haemorrhage (IVH), and convulsions (Wilcox et al., 1996). The later development of infants from higher multiple births frequently exhibit developmental delay, cerebral palsy, visual and hearing disorders (Botting et al., 1987; Gonen et al., 1990). The social aspects of higher multiple births have been largely neglected. After birth, the couples often are left alone with their problems. Once the children are at home, the troubles mount: lack of space and of sleep for the parents, need for extra help to meet the needs of all the children, and an unexpected strain on the family's finances (Levene, 1991). Few systematic follow-up studies in families after assisted reproduction have been published. It seems that children from multiple births live in suboptimal conditions more frequently than singletons: Parents of twins conceived through IVF reported significantly higher levels of stress associated with parenting than those with naturally conceived twins, due to increased expectations on themselves (Cook et al., 1998). Mothers of triplets feel isolated, overburdened, depressed, are overprotective, and need psychotherapeutic support (Garel and Blondel, 1993). The risk of depression increases with the number of multiples (Thorpe et al., 1991). In some families, severe problems with the partner arise after birth, and pre-existing psychopathological disorders may be aggravated. The prognosis for parents and children is often disappointing. The roles, responsibilities, loyalties, and ethics of physicians are visibly changing in the increasingly cost-conscious era of managed care (Kassirer, 1998). It is surprising to realize that in reproductive medicine, the cost–benefit relationship may be profoundly neglected. The insurance companies normally take charge of four IVF procedures and two GIFT procedures (cost for each procedure US$2450–3680 in Germany). The success rates are only 10–30% per embryo transfer depending on the technique used and on the woman's age. Transferring three, rather than two embryos, does not increase the pregnancy rate, but increases the risk of multiple gestation (Templeton and Morris, 1998). The implantation rate of blastocysts, on the other hand, may be >40% (Gardner et al., 1998). If complications or preterm delivery occur as in the cases described, the cost for maternal hospitalization and for neonatal intensive care must be added. Callahan et al. (1994) showed how multiple gestation pregnancies resulting from assisted reproduction dramatically increase immediate postnatal hospital charges. Furthermore, increased lifetime cost for medical care, rehabilitation, and special education of disabled children must be added to this calculation. Even economically German families are when they have triplets. However, migrant couples have problems due to their social surroundings with to childlessness. Islamic women whose lives are reduced by the in an frequently hope to their by birth to more children. The desire for a child more than other problems as the of the marriage, of or the financial reproductive are that even couples whose mother is German may not understand Many Turkish women school for only a years. these in with the these women are unable to understand the information given to In Turkish there is no education. have a different of than the between and is and they and more medical treatment (Yüksel et al., without any knowledge of the premature multiple Islamic women infertility treatment much earlier and are at an increased risk of multiple pregnancies. Ovulation drugs are more in young women who have been from infertility for only a In the IVF success rate per is in women years (SART/ASRM, 1998). cannot the of higher order multiple gestation and must the of more disabled children, if current treatment Health and must their and expectations and realize that there are than not must to the risk of multiple pregnancies to a even if the result is a pregnancy high pregnancy rates are and as the of treatment multiple are frequently success with risk of multiple gestation, an treatment take into the age and treatment of the as the of the embryos transferred The German for reproductive are to transfer only two embryos per cycle for women years. and other have to the risk of multiple pregnancy an pregnancy aim to embryo and of and to implantation for embryos Despite the of multiple with problems a desire for multiple births which increases with age et al., 1995). The length of infertility is with the to a multiple even triplets. infertile failure is as a pregnancy and more detailed is to the the risk of multiple births in and to to the of children, has for and We not believe that these be to infertile couples help to their desire for a child. However, believe that must be to and for families indicated in our case on assisted reproduction cannot be to with to the of the but must include medical, psychological, and social aspects of multiple gestation and preterm In migrant an the husband or that the woman the and to only one and as or be by the counselling. professional in assisted reproduction. In Turkish migrants in counselling be since most of these couples are already severely by the social conflicts with assisted reproduction is to families with the medical, and of this treatment cannot be than one reproductive must the of the which children to be born. risk index for babies was developed as of hospital and developmental are given for birthweight, gestational and during the first 12 h, and of Griffiths of children's quotient was derived by the score hearing to the corrected age. has been reported to be at 12 and at 20 months corrected was as a severe as threshold was measured auditory brain stem evoked for and was as the intensity at which could be quadruplets at 25 weeks gestation. of problems quadruplets at 25 weeks gestation. of problems triplets at 26 weeks gestation. of problems triplets at 26 weeks gestation. of problems