Obstetric outcome and psychological follow-up of pregnancies after embryo reduction

Christina Bergh1,3, Anders Möller1, Lars Nilsson1 and Matts Wikland2

1 Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Göteborg University, S-413 45 Göteborg and 2 Fertility Centre, Carlanderska Hospital, Göteborg, Sweden


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The obstetric outcome and psychological follow-up of the parents after embryo reduction performed at Sahlgrenska University Hospital between 1993 and 1997 in 13 women treated for infertility is described. A comparison is made with non-reduced multiple pregnancies, both spontaneous and multiple pregnancies after assisted reproduction technology. Altogether 10 triplets, two quadruplets and one quintuplet pregnancy underwent embryo reduction. The surgical procedure was performed in gestation week 7–8 by transvaginal, ultrasound-guided aspiration of embryonic tissue. The psychological follow-up included personal interviews and psychological evaluations by a Psychological General Well-being Scale (PGWB) and Beck's Depression Inventory (BDI). In 11 cases reduction was performed to twin pregnancies. In two cases of triplets after in-vitro fertilization and transfer of two embryos, reduction was performed on the monozygotic, monochorionic twins. No complete miscarriages occurred. Ten women delivered twins and three women delivered singletons. The mean gestation length was 40.4 weeks for singletons and 35.9 weeks for twins. The mean birthweight was 3411 g for singletons and 2392 g for twins. No complications related to the reduction were detected in the children.The psychological follow-up showed that the psychological well-being of the parents was good. However, the events around the reduction were experienced as chaotic and emotionally disturbing. One woman regretted the reduction. All couples emphasized that avoidance of high order pregnancies should be of primary importance. In conclusion, embryo reduction appears to improve the perinatal outcome of multiple pregnancies obtained after assisted reproduction technology. It is important that the surgical procedure is performed at a centre with experience of this type of intervention, by a limited number of surgeons and in a regulated manner. Psychologically, however, the intervention is traumatic and psychological management is essential for good final outcome.

Key words: embryo reduction/multifetal pregnancy/psychological follow-up


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In recent years, the use of ovulation induction and assisted reproductive technology has allowed thousands of otherwise childless couples to have children of their own. In parallel, however, the frequency of multiple pregnancies has increased dramatically world-wide. The risks associated with multifetal pregnancies include increased perinatal mortality and morbidity, maternal pregnancy complications, emotional distress such as fatigue, stress and depression (Garel et al., 1997bGo) and socio-economic problems. These risks exist also for twins compared to singletons and efforts to decrease the number of multiple pregnancies must be regarded as one of the most important tasks for all physicians and scientists working in the field of reproduction. Methods to reach this goal should include extreme care when monitoring ovulation induction and limiting the number of embryos transferred in in-vitro fertilization (IVF)/embryo transfer to primarily one embryo and occasionally two. Internationally, embryo reduction has been used as an option in cases with multifetal pregnancies. Collaborative experience has demonstrated a satisfactory outcome for the children and limited risks for the mother (Evans, 1996Go). Although the medical aspects of multifetal pregnancy reduction (MFPR) are rather well known and have been described in several publications, the psychological reactions of parents, their subsequent bonding behaviour and the development of the children have rarely been investigated. It might be expected that women undergoing MFPR are at risk for psychological problems. Almost all of these women have a history of long-standing infertility, and having to terminate much desired fetuses might be experienced as very painful emotionally and provoke acute and prolonged grief reactions to the reduction. Since the reduction is self-decided, emotional reactions might also be more severe compared to women with infertility who spontaneously miscarry or to women who undergo abortion for genetic reasons. Feelings of guilt, grief and mourning (Kanhai et al., 1994Go), emotional pain, depressive reactions, fear and stress (Schreiner-Engel et al., 1995Go) in connection with the reduction have been reported. This study describes the outcome after embryo reduction during a certain time period, focusing on the psychological consequences. The report includes a limited number of patients since multiple pregnancies of high grade occur rather seldom in Scandinavia due to a restrictive policy of transferring only two embryos in a majority of IVF cycles. In any case, these multiple pregnancies constitute a serious problem.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Between 1993 and 1997, 13 patients with multifetal pregnancies underwent embryo reduction at the Unit of Reproductive Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. In six cases ovulation induction and in seven cases IVF/embryo transfer with transfer of two or three embryos was performed. All IVF cases and four out of six ovulation induction cases were primarily treated at Sahlgrenska University Hospital or the Fertility Centre, Carlanderska Hospital, Göteborg and the remaining two cases were referred from hospitals in the Western part of Sweden. During the study period, 1993 to 1997, all patients treated at the two hospitals in Göteborg who conceived multifetal pregnancies were informed about and offered embryo reduction. In addition to the 13 women undergoing embryo reduction, three other cases of triplets occurred at the two hospitals. Two of these women were offered embryo reduction but declined while the triplet of the third woman was only detected in the late second trimester and fetal reduction was not recommended. Couples considering reduction attended an initial 1 h medical counselling session at least one day before the reduction with the surgeon who was to perform the procedure. All risks, including the risk of complete miscarriage and the risk of a repeated surgical procedure in case of non-successful reduction, were explained. Possible benefits were also discussed and the patients' questions and concerns were fully addressed.

The average length of co-habiting in the study group was 10 years (7–15 years). Two of the couples already had two children each, one couple had one child while the remaining couples were childless. The duration of their infertility ranged from 1 to 7 years. All men and women were considered well educated, above average for Sweden, and 16 of the 26 had received a university education. Six couples were living in cities and the others in villages or rural areas.

The surgical technique applied in this series was mechanical destruction of the embryo by early transvaginal puncture under ultrasound guidance, as described (Vauthier-Brouzes and Lefebvre, 1992Go). The embryo reductions were performed under general anaesthesia in gestation week 7 to 8.5, by one physician (C.B.). Briefly, thorough vaginal cleansing with chlorhexidine followed by sterile saline solution was performed. Prophylactic antibiotic, 1.5 mg cefuroxime (Zinacef, Glaxo Wellcome), was given before the procedure and then twice with 8 h in between. A 7 MHz transvaginal transducer equipped with a puncturing guide was used and a 25 cm long needle with a 1.6 mm outer diameter was advanced through the vaginal fornix and the uterine wall into the most easily accessible sac. The needle tip was inserted into the thoracic cavity of the embryo and careful aspiration under ultrasound guidance was performed, resulting in complete or partial disappearance of the embryonic echo. The amniotic fluid was not aspirated, in order to facilitate subsequent ultrasound monitoring. Reduction was generally performed on the sacs implanted in the lowest part of the uterine cavity or in those with obvious growth retardation. In two cases, with triplets after IVF and transfer of two embryos, the monozygotic, monochorionic twins were chosen for reduction. In all other cases, two embryos were left in place. The women stayed in hospital overnight and ultrasound scanning was repeated the following morning before discharge. Further ultrasound scanning was performed weekly for the following 2 weeks, then according to the routine antenatal programme until delivery.

A psychological follow-up was performed on the 13 couples who underwent embryo reduction as well as the two couples who declined reduction. The follow-up took place between 2.5 months and 4 years after the delivery and the two main questions were: (i) how was the psychological health of the women and men at the time of the interview; (ii) how did the women and men experience the process related to the reduction? Patients were invited to participate in the psychological follow-up by a letter from the physician who performed the embryo reduction. The letter described the purpose of the follow-up study and presented the psychologist who would perform the interviews and the psychological tests. The physician then called each patient and asked for consent to inclusion. The interviews and the tests were scheduled by the interviewer and later carried out as personal visits. Personal interviews and evaluation by a Psychological General Well-being Scale (PGWB) (Dupey in Wenger et al., 1984) and Beck's Depression Inventory (BDI) (Beck and Steer, 1987) were utilized. PGWB measures general psychological well-being with 22 items with six response alternatives (1–6). The higher value, the better well-being. The scale is constructed so that, in addition to a total score, subscores can be given for anxiety, depressed mood, positive well-being, self-control, general health and vitality. BDI is probably the most frequently used self-rating scale for measuring depression. The response alternatives are arranged by degree of difficulty. High values indicate more severe depression. Values are given for the normal range: 0–9; mild–moderate depression: 10–18; moderate–severe depression: 19–29; and extremely severe depression: 30–63. Both scales have been translated into Swedish and tested on Swedish patients (Jansson, 1986Go; Dimenäs et al., 1996Go). They are also well documented from a psychometric viewpoint and have been found to have reliability and validity (Dupey, 1984Go; Beck and Steer, 1987).

The personal interviews examined the couple's way of coping with the embryo reduction before and after the surgery. The following topics were covered by the interviews: experiences from the infertile period, reactions to the information about multiple gestation and the possibility of performing an embryo reduction, thoughts and feelings before and after the reduction, the interaction between man and woman, and the interaction with social surroundings.

The two couples that declined embryo reduction were interviewed about the same topics as the couples who underwent reduction. They described their thoughts and feelings related to their decision to decline reduction.

The interviews were performed in a narrative way. The couples were encouraged to relate their experiences following the discovery of the multiple pregnancy, via decision-making and surgery (or declination) to the period afterwards. The interviews were performed with the couple together, but the man and woman filled in the self-rating scales separately.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Obstetric outcome
The infertility treatment resulted in 10 triplets, two quadruplets and one quintuplet. In 11 cases reduction was performed on twins and in two cases monozygotic/monochorionic twin reduction was performed. In two pregnancies, reduced to twins, one fetus died in utero in trimester II and III respectively, and these women later delivered singletons at term. No complete miscarriages occurred. Nine women have delivered twins and four women singletons. The mean gestation length was 40.4 weeks for singletons and 35.9 weeks for twins (Table IGo). The mean birthweight was 3411 g for singletons and 2392 g for twins (Table IIGo). The mean gestation length and the mean birthweight for IVF children, treated at Sahlgrenska Hospital between 1990 and 1995 and children from the Swedish Medical Birth Registry, are presented for comparison. No complications related to the reduction were detected in the children. In one child, from the quintuplet pregnancy reduced to twins and where one fetus died in utero in trimester II, a chromosome anomaly was detected at 6 months of age [46XY,del(15q11–13), consistent with Prader–Willis syndrome]. In another child, screening for phenylketonuria showed a positive result. This child is now doing well on a diet. A third child suffered severe intrapartum asphyxia, due to placental abruption. The development of this child is, however, satisfactory, although the ultimate outcome cannot yet be fully evaluated.


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Table I. Gestational length, weeks (mean ± SD)
 

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Table II. Birthweight, g (mean ± SD)
 
Psychological follow-up
All 26 persons who underwent embryo reduction felt psychologically well at the time of interview as assessed by the interviews and the self-rating scales. They showed no signs of depression. Their values according to BDI varied between 0 and 8 points. Nor did they show any signs of other psychological distress. On the contrary, they all had a good psychological well-being according to PGWB. Their mean total scores were 106 (range 98–120). In comparison, a Swedish study among healthy men and women, aged 20–30 years and 30–40 years respectively, showed scores of 104.0–101.1 and 100.8–97.9 when expressed as 95% confidence intervals (Dimenäs et al., 1996Go). As expected, all parents were often tired and had difficulties getting restful sleep. Nine women and three men reported less interest in sex. A majority of the couples (10 couples) described the period of infertility as troublesome and three couples described themselves as resigned to infertility. All couples became very happy when informed about the pregnancy. The reaction to the information about more than two gestation sacs was often described in terms of shock and tumult. Two couples also expressed positive feelings on learning this information — `we were pregnant after all'. The first reactions to possible embryo reduction included both fear of losing all embryos and recognition of the lack of alternative. All couples stated that they immediately started a process of risk analysis where the pros and cons of the different alternatives were weighed. The need for a fast decision was very stressful. The decision process and performance of the reduction was different for the couples. Four of them stated that they very quickly decided upon the reduction and that it was rather uncomplicated. The other couples described anguish. Being forced to abort one or two embryos, which are potential children, after having fought so hard to become pregnant, was considered absurd. The question `is it ethically right to take a life in order to increase the chances for another?' was raised by some couples as well as the question whether we should decide in situations where we perhaps should remain passive. Some couples said that what initially seemed obvious later was not that obvious after all. Nine couples explained that it was relatively easy to reach a decision, even though they had ethical objections, whereas four couples found the decision very difficult. The agreement between man and woman was very high. Before the reduction, 11 couples (mainly the women) were afraid or nervous whereas two felt calm. Eight couples reported that they felt comfortable after the procedure. One woman sobbed and said that she felt grief in her heart; in one case the surgery had to be repeated, which was considered a disaster, making this woman anxious during the whole gestation; in two cases one fetus died in utero; one woman regretted the procedure deeply afterwards.

Thoughts and feelings after the surgery were different for different couples. A majority of the couples had thoughts about what the children would have looked like if they had been born, how it would have been if they had aborted one of the now living children, how it would have been to have had triplets, particularly when they read about triplets, and also when their existing children demanding more attention.

One couple had not told anyone about the embryo reduction. Six couples had told their closest relatives and friends, while the others had told everyone. Some couples reported that people sometimes reacted in a nervous way when informed about the reduction. All couples thought they had received good and reliable information and that they were met in a positive way in connection with ultrasound investigation and surgical procedures. Critical remarks were made about the lack of information before infertility treatment concerning the risk of high order multiple pregnancy.

All except one woman believed they had made the right decision when deciding upon reduction and all except two women would make the same decision again if necessary. All couples, however, emphasized that it is important to avoid situations where embryo reduction is required. The process covered by the interviews was accompanied by strong and often mixed and contradictory feelings. Feelings of happiness for the pregnancies were present together with feelings of anxiety for the related medical risks and later also feelings of grief for the aborted embryo(s). Several couples emotionally both wanted to keep all embryos (potential children) and still had to decide about reduction for so-called rational reasons. All couples explained that the happiness of getting a child (children) overshadowed the problems related to the reduction.

Non-reduced pregnancies
Regarding the two couples who declined reduction, one of them delivered triplets in gestation week 37, after an uncomplicated pregnancy. All three children were healthy and developed well. Their parents also felt well. The other couple delivered in gestation week 26. The monozygotic twins died neonatally while the third child was healthy and has developed normally. The woman in this couple suffered from some depressive reactions and they still mourn their two dead children. The first couple stated that the decision to decline embryo reduction was extremely difficult, having to evaluate both the risks associated with reduction and those associated with continuing the triplet pregnancy. Their observation of fetal movements on ultrasound examination supported their decision to decline reduction. The second couple immediately felt that they did not want to undergo embryo reduction. As no signs of fetal abnormality were observed at ultrasound investigation, they preferred to continue the triplet pregnancy and felt sure they would be able to cope with the situation. Neither of these couples regretted their decision. The couple which lost two children neonatally declared that their grief after this loss was probably more real than it would have been if embryo reduction had been performed.


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Since the first published reports of MFPR (Dumez and Oury, 1986Go; Kanhai et al., 1986Go) several large series of MFPR have been published (Wapner et al., 1990Go; Dommergues et al., 1994Go; Evans et al., 1994Go, 1996Go; Maymon et al., 1995Go). In a great majority of these publications MFPR has been performed early in gestation but late selective MFPR performed in gestational week 14–29 has been reported (Hartoov et al., 1998Go). Although it is widely accepted that multifetal reduction reduces the obstetric and perinatal risks for pregnancies with four or more fetuses, no consensus exists for triplets. Data on the natural history of triplets suggest that the mean gestational age at delivery is generally around 33 weeks. In a study comparing the outcome of twins versus triplets, a significantly higher incidence of preterm delivery, growth retardation and requirement of neonatal intensive care was found for triplets (Sasson et al., 1990Go). Although the mean gestation length was 33.0 weeks versus 36.6 weeks and the birthweight 1720 versus 2475 g for triplets compared to twins, no significant differences could be found in neonatal morbidity and mortality in this study. However, in a population-based study of cerebral palsy in Australia (Petterson et al., 1990Go) a prevalence rate for cerebral palsy of 2.4 per 1000 for singletons, 6.3 per 1000 for twins and 32 per 1000 for triplets was found.

The obstetric outcome after embryo reduction in the present series showed that the birthweight and gestation length were comparable to those for non-reduced twin pregnancies, both after IVF and according to the Swedish Medical Birth Registry (SMBR). The birthweight was 600–700 g higher after reduction to twins compared to non-reduced triplets and the gestation length was 3–4 weeks longer. This is in accordance with earlier publications (Macones et al., 1993Go; Lipitz et al., 1996Go). In a recent study, however, a slightly less positive outcome after reduction to twins compared to non-reduced twins (Sebire et al., 1997Go) was found.

The main risk in embryo reduction is miscarriage. In the present series, no complete miscarriage occurred. Overall, a pregnancy loss of 11.7% was reported in a large multicentre study including 1789 cases of multifetal reduction (Evans et al., 1996Go). A strong correlation between starting number, finishing number and likelihood of poor outcome for both pregnancy loss and prematurity was detected. The lowest pregnancy loss was found for cases reduced to twins, with increasing losses for singletons, higher still for triplets. However, the rate of premature delivery was lowest with singletons. Accordingly, the mean gestation length at delivery was highest for pregnancies reduced to singletons. In individual series, however, the miscarriage rate has varied between 0 and 40% (Shalev et al., 1989Go; Rådestad et al., 1996Go). It is also of importance to note that in a prospective study comparing the outcome of triplet pregnancies managed expectantly or by multifetal reduction the spontaneous pregnancy loss before 24 weeks was 20.7% (Lipitz et al., 1994Go).

In the present study, all pregnancies were reduced to twins except for two pregnancies reduced to singletons. These two pregnancies occurred after transfer of two embryos and were thus monozygotic. It has clearly been shown that both monozygotic fetuses should be terminated or left alone because of the high probability of vascular connections between the placentas of the monochoriotic twins. Selective termination of one twin may thus cause death or severe damage to the co-twin (Wapner et al., 1990Go).

Two major techniques for embryo reduction have been described; the transabdominal, ultrasound-guided approach with injection into the fetal thorax of a cardiotoxic agent such as KCl or hypertonic saline, performed in gestation week 9–12 (Berkowitz et al., 1988; Shalev et al., 1989Go), and transvaginal, ultrasound-guided aspiration performed at an earlier gestation age. The technique used for embryo reduction in the present study was early ultrasound-guided transvaginal aspiration (Itskowitz-Eldor et al., 1992) and further used by Vauthier-Brouzes and Lefebvres (1992). The advantage of this technique compared to the transabdominal approach is the small embryonic size at this early stage of gestation, rendering the embryo more fragile to needle aspiration with no need for injection of cardiotoxic agents. Toxic effects of KCl and hypertonic saline on the remaining fetuses have been reported (Boulot et al., 1990Go; Tabsh et al., 1990Go; Wapner et al., 1990Go). The early intervention may also be favourable. A negative association has been found between the gestational age at reduction and gestation length at delivery, presumably reflecting the amount of dead feto-placental tissue (Sebire et al., 1997Go). Performing the procedure very early in the pregnancy may also make it easier for the couple to accept it. An additional reason for choosing the transvaginal technique was the surgeons' familiarity with it, due to the similarity with IVF oocyte recovery and use of the same equipment.

In the present study the psychological reactions to embryo reduction were thoroughly investigated. In addition to personal interviews by a psychologist, using semi-structured questionnaires, two psychological evaluation tests were used. In all aspects both partners were investigated. The small number of patients did not allow any statistical analysis. Instead the results are presented in a more narrative way.

In two earlier studies, both from the USA (McKinney et al., 1995Go; Schreiner-Engel et al., 1995Go) 91 and 42 women respectively were investigated solely using telephone interviews. Both studies reported that most women remembered the reduction as very stressful, very painful emotionally and very frightening. Feelings of guilt and sadness were frequently noticed, although severe depressive symptoms seldom occurred. Both studies concluded that although MFPR is highly stressful, the psychiatric risks of the medical intervention are low for a majority of the patients. In a study from Holland (Kanhai et al., 1994Go), 21 couples undergoing MFPR were investigated. Patients were visited at home by a psychologist and both parents were interviewed, using semi-structured questionnaires. Although there had been immediate feelings of guilt and sadness, no serious adverse effects were noted at the time of the interview. However, a majority of the women stated that they had been unaware of the risks and consequences of infertility treatment. Thus, the study demonstrated the need for adequate information before infertility treatment. In a French study (Garel et al., 1997aGo) 18 women undergoing MFPR were included. Comparison was made with 11 women from a previous study (Garel et al., 1997bGo) not undergoing fetal reduction and delivering triplets. The mothers were investigated by semi-structured interviews at home. At 1 year after delivery, one-third of the women in the reduction group reported persistent depressive symptoms related to the reduction. These symptoms had disappeared for all but two women at 2 years. The comparison with families having triplets indicated that, 2 years after delivery, the mothers' psychological health and their relationship with the children were more satisfactory in the reduction group. However, the interpretation of the observations in this study presented obvious difficulties since almost 50% of the women in the reduction group were lost to follow-up because of refusals to participate in the study, miscarriages or having moved abroad. There were no refusals in the triplet group. As a comparison, in the study of triplets (Garel et al., 1997bGo) all 11 women suffered emotional distress, mainly fatigue and stress, 4 years after delivery. In addition, four of the mothers were clinically depressed. The psychological follow-up in this study showed that both the women and the men were feeling psychologically well. They were judged not to have been psychologically injured by their experiences and the embryo reduction had not increased their psychiatric morbidity. It was evident, however, that even though the couples felt they had made the right decision, the experience was very stressful, thus emphasizing the importance of avoiding the situation. All couples were very grateful for having a child (children) at last and for the physicians' help in this respect. The experience of the couples that declined reduction emphasizes the importance of giving the couple a real opportunity to chose or decline embryo reduction. It could be argued that the rather large variation in time between the embryo reduction and the psychological follow-up might have influenced the results of the psychological evaluation. It is possible that a longer time period between the surgical intervention and the interviews would decrease the negative feelings associated with this procedure. However, no comparison was actually performed between the different patients. The main feelings associated with the reduction such as anxiety, sadness, grief and guilt seemed rather constant from patient to patient and independent of the time point of the psychological evaluation.

Although most physicians working with assisted reproductive technology are extremely cautious in their use of these new techniques, there have been reports of people including embryo reduction as part of an extremely aggressive programme with transfer of several cleaved embryos in order to optimize pregnancy rates without discussion of the ethical consequences (Ayers et al., 1991Go).

In conclusion, the selective, transvaginal, ultrasound-guided embryo reduction technique, performed after 7–8 weeks of amenorrhoea, is in our opinion a safe technique with a low miscarriage rate and limited risks for the remaining fetuses. It should be performed at a centre with experience and by a limited number of surgeons. The psychological care of these couples throughout the process is extremely important. Even though no serious psychiatric morbidity was detected in our patients, it is our definite impression that MFPR is an extremely stressful situation for the couple. It should not be included as a routine part of assisted reproductive technology but only used in exceptional cases. Physicians working in this field must be aware of all consequences of multifetal pregnancies and assume greater responsibility not only for establishment of a pregnancy but also for the course of the pregnancy and for the future of the newborn infant. More efforts should be made on minimizing the risks of multiple pregnancies after assisted reproductive technology even if this means a slight decline in pregnancy rate per cycle. In fact, elective transfer of a single embryo in 67 women in a Finnish study was recently found to give a satisfactory pregnancy rate of 28.4% per transfer (Vilska et al., 1998Go).


    Acknowledgments
 
This study was supported by the Hjalmar Svensson Foundation and the Göteborg University.


    Notes
 
3 To whom correspondence should be addressed Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
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Submitted on March 5, 1999; accepted on May 20, 1999.