Hum. Reprod. Advance Access published online on July 29, 2008
Human Reproduction, doi:10.1093/humrep/den291
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Attitude of women with IVF and spontaneous pregnancies towards prenatal screening
Department of Obstetrics and Gynecology, American University of Beirut Medical Center, PO Box: 113-6044-6A, Beirut, Lebanon
1 Correspondence address. Tel: +961-3-310855; Fax: +961-1-370829; E-mail: aa06{at}aub.edu.lb
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Abstract |
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BACKGROUND: Factors influencing a pregnant woman’s decision to accept prenatal testing are largely undefined. Our study aimed to compare the acceptance rate of prenatal diagnosis in women who conceived through IVF or ICSI (cases) with that of women who conceived spontaneously (controls).
METHODS: Retrospective chart review in Lebanon of all primiparas carrying singletons who were offered prenatal testing (triple screen/amniocentesis) from 2004–2007. The influence of IVF/ICSI on the acceptance of prenatal screening was evaluated.
RESULTS: 336 pregnant women were offered prenatal testing (120 cases and 216 controls). Cases were less likely to perform prenatal testing compared with controls (52.5 versus 72.7%; P < 0.001). The rate of utilization of prenatal testing was independent of the infertility cause. Multiple logistic regression analysis revealed that women who conceived through IVF/ICSI [odds ratio (OR) 0.427, 95% confidence interval (CI) 0.252–0.724], those 
35 years old (OR 0.184, 95% CI 0.102–0.329) and lower socioeconomic class (OR 0.339, 95% CI 0.197–0.584) were less likely to perform triple screen test, and women who conceived through IVF/ICSI (OR 0.354, 95% CI 0.131–0.958) and those of lower socioeconomic class (OR 0.113, 95% CI 0.033–0.403) were less likely to perform amniocentesis.
CONCLUSIONS: There was a significant difference in acceptance rate of prenatal diagnostic testing between women who conceived through IVF/ICSI and those who conceived spontaneously. Women who conceived through IVF/ICSI were less likely to opt for prenatal diagnosis even after controlling for confounding variables.
Key words: IVF/triple screen/amniocentesis/spontaneous pregnancy
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Introduction |
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Many women who undergo assisted reproduction technology (ART) are over 35 years of age, either because of years spent attempting pregnancy or because of conscious choice to delay childbearing (Ragni et al., 2005
). This puts their offspring at an increased risk of aneuoploidy (Schover et al., 1998) which is known to increase with age 35 years (Jorde et al., 1995). Advanced paternal age also may contribute to genetic risks, although genetic counseling and prenatal diagnosis are usually not advised until the male partner is over age 55 years. Karyotype is reported to be abnormal in 8–15% of azoospermic men (Wilkins-Haug et al., 1997) and 6% of those with sperm counts <10 million/ml. Microdeletions of the Y chromosome have also been diagnosed in 10–15% of men with severe oligospermia (Pryor et al., 1997). In addition, children born following ART or infertility treatment and those born after long periods of infertility are at increased risk of birth defects compared with spontaneous conceptions (Hansen et al., 2005; Zhu et al., 2006). Because of all these risks, many centers offer karyotyping for all men with oligozoospermia or azoospermia of unknown etiology (Wilkins-Haug et al., 1997) and offer genetic counseling and prenatal diagnosis to all couples undergoing ICSI.
Nowadays, prenatal diagnostic testing using triple (alpha fetoprotein, beta-hCG and unconjugated estriol) or quadruple serum analytes and amniocentesis are offered routinely to pregnant women at risk of chromosomal abnormalities. While serum analysis does not entail any risk to the mother or her fetus, amniocentesis is associated with several complications. These include fetal loss rates reaching 0.5% (Nassar et al., 2004; Gardner and Sutherland, 1996; ACOG, 2001), vaginal spotting or amniotic fluid leak in 
1–2% of cases, and chorioamnionitis in less than 1 in 1000 cases (Gardner and Sutherland, 1996; ACOG, 2001).
Factors that influence a pregnant woman’s decision to accept or decline genetic amniocentesis are largely undefined and are usually based on ill-supported data or personal experiences. Among these factors are the method of conception, age, parity, consanguinity, family history of congenital anomalies, history of miscarriage, twin gestation, socioeconomic background and religion. A study by Schover et al. (1996) suggested that couples choosing ICSI have a very strong desire for ‘genetic’ children and have little concern about genetic risk factors. Women who undergo IVF might theoretically be hesitant to perform genetic amniocentesis because of the attributed risk of miscarriage. Conversely, some may seek the added assurance of karyotypically normal pregnancies following their history of infertility. How these conflicting factors may affect a pregnant woman’s decision to accept prenatal diagnosis is largely unknown. Health care providers, on the basis of the above perceptions, may offer differential counseling about prenatal diagnosis.
The Lebanese health system is private and prenatal diagnostic procedures are currently available in Lebanon in specialized centers. Lebanon is a mosaic of different religious communities which can be grouped broadly into Moslems, Christians or Druze. Previous studies have reported that the most critical factor which determines the acceptability of prenatal diagnosis and termination of pregnancy in case of an affected fetus seems to be religious conviction of the couple at risk (Zahed et al., 1999). Neither the genetic risk of the couple nor the cost of the procedure in a private health system seem to be factors of major importance. Acceptability of prenatal diagnosis decreases with lower socioeconomic status and lower educational background, two variables which are usually correlated in Lebanon. Another important feature in our population is the poor understanding couples have of their genetic risk. In a study by Zahed et al. (1999) only 12.2% of couples interviewed were accurately aware of their genetic risk. While western medicine has evolved to encourage autonomous informed decisions, such methods of practice are not necessarily applicable to Lebanon. Discussing probability, offering alternatives and not providing a firm recommendation are frequently interpreted as signs of self-doubt and lack of medical knowledge by many Lebanese patients (Eldahdah et al., 2007). In Lebanon, 37% of obstetricians are reported to encourage their patients to consider undergoing or foregoing prenatal diagnosis (Eldahdah et al., 2007).
Under Lebanese law, abortion for medical reasons is legal only if the mother’s health is at risk. Despite that, therapeutic abortion of abnormal pregnancies has some level of approval by the medical community and is being practiced in a private setting. In fact, rates of termination of pregnancies with Down’s syndrome and sex chromosome anomalies are comparable to those reported in other countries (Eldahdah et al., 2007). In addition, 80% of Lebanese physicians would personally terminate a pregnancy affected with Down’s syndrome (Zahed et al., 2002).
In many Middle Eastern countries, including Lebanon, there is a stigma attached to families who have a child with a disability. These families complain of isolation and lack of community resources to help them cope with their circumstances and optimize the child’s abilities. Although there have been some improvements in how the society in Lebanon perceives intellectual disability, most mothers prefer to isolate themselves and keep their child at home to avoid stigmatization and criticism (Azar et al., 2006).
The aim of the present study was to compare the rate of acceptance of prenatal diagnosis in Lebanese women who conceived through IVF/ICSI with that of women who conceived naturally.
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Materials and Methods |
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This was a retrospective review of medical records of all singleton primiparous women who were offered prenatal diagnostic testing and delivered by one obstetrician (A.A.M.) at the American University of Beirut Medical Center between January 2004 and June 2007.
Women who had booked for prenatal care with A.A.M. and reached 15 weeks of pregnancy were included. Excluded were women with a history of fetal chromosomal abnormalities or any fetal structural anomalies, history of recurrent abortions and multiple gestation. On their first antenatal visit, information about religion, insurance coverage, family and reproductive history, awareness of genetic risk and prenatal diagnostic procedures was collected. Socioeconomic status was determined based on the third-party coverage, with patients admitted at the expense of the ministry of health classified as low socioeconomic status, and those who had private insurance classified as high socioeconomic status. Maternal age, accurate dating by first trimester ultrasound, family history of chromosomal or genetic disorders, history of miscarriage or abortions and ultrasound findings were documented. Patients were informed by A.A.M. about the availability of the triple screen test and its timing (15–20 weeks for triple screen test and amniocentesis) and were counseled about the limitations of the triple screen test, the need for further testing by amniocentesis in the event of abnormal results, and their options if amniocentesis results confirmed aneuploidy. They were also counseled about the risks associated with amniocentesis including fetal loss, vaginal spotting, amniotic fluid leak and chorioamnionitis. In addition, the benefits, risks, limitations and alternatives to genetic amniocentesis were explored with the women and their partners when appropriate. At 13–15 weeks of gestation, the couple was asked whether they had any questions regarding either test and whether they made a decision for or against performing any of these tests. Couples declining to perform the tests were encouraged to freely express their attitude and to give, when possible, reasons for refusing the tests by using an open-ended question. Reasons were grouped into four categories. The religious reasons included responses like ‘whatever God sends is acceptable’, ‘rely on God for sending a healthy child’ or ‘refuse abortion because it is forbidden by religion’. Anxiety included responses like ‘do not want to know’ or ‘do not want to worry about the result’. The other remaining categories were financial and unspecified. Those who accepted genetic amniocentesis were referred to a perinatologist to perform the procedure. Results were communicated to the patients by phone, and those with abnormal findings or more questions were scheduled for a post-amniocentesis counseling session to review their options and further plans for the pregnancy. Institutional Review Board approval was obtained for the study.
Distributional characteristics of the variables were examined. Patients were divided into those who conceived through IVF or ICSI and those with spontaneous pregnancies. The two groups were compared regarding the reasons for declining to perform amniocentesis or triple screen test. Differences between groups were examined using the Student's t-test for continuous variables and 
2 test for categorical data. Multivariate logistic regression analysis was performed to examine the influence of different variables on the rate of acceptance of prenatal diagnostic tests. All tests of significance were two-sided at a critical level of 0.05.
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Results |
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A total of 120 pregnancies which were the product of IVF/ICSI and 216 spontaneous pregnancies were included in the study. The cause of infertility in women undergoing IVF/ICSI was male factor (n = 88, 73.3%), female factor (n = 14, 11.7%) and unexplained (n = 18, 15.0%).
Comparing spontaneous with IVF/ICSI pregnancies, IVF/ICSI pregnancies had a higher mean maternal age (32.6 ± 5.0 versus 30.7 ± 4.7 years, P < 0.001) with a higher proportion of women 35 years (36.7 versus 22.7%, P = 0.009). The two groups had a similar socioeconomic background and religious distribution (Moslems, Christians or Druze).
Table I shows the rate of utilization of triple screen test and amniocentesis in the two groups. Women who conceived by IVF/ICSI were less likely to perform either test compared with those who had spontaneous pregnancies despite the higher mean age and proportion of patients 35 years. This also tended to be true in the subgroup of women 35 years of age, although differences did not reach statistical significance.
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Table II shows the rate of acceptance of prenatal diagnostic tests in IVF patients according to the cause of infertility. Those with male factor and unexplained infertility used triple screen test more frequently than those with female factor, wheras those with female factor were more likely to undergo amniocentesis than those with male factor.
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Table III summarizes the reasons for declining prenatal diagnostic testing in the two groups and Table IV shows the distribution of demographic variables according to whether women accepted or declined a prenatal diagnostic test. IVF/ICSI patients were over-represented in the subgroup of patients who declined triple screen test and either amniocentesis or triple screen test. Patients
35 years of age were more frequent in the subgroup of patients that underwent amniocentesis but less frequent in those that underwent triple screen test. Private patients more frequently performed both prenatal diagnostic tests. Moslems were under-represented in the subgroup of patients that underwent triple screen test or either test while the opposite was true for Christians.
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Table V shows the result of the multiple logistic regression analysis of the rate of acceptance of prenatal diagnostic tests. Variables that were entered in the model were IVF/ICSI, socioeconomic class, age
35 years and religion (Moslem, Christian or Druze). IVF/ICSI patients, those with advanced age and lower socioeconomic class were less likely to perform triple screen test, whereas Christians were more likely to perform the triple screen test than Moslems. IVF patients and those of lower socioeconomic class were less likely to perform amniocentesis, whereas religion had no impact on the rate of utilization of amniocentesis. When women 35 years of age were deleted from the model, IVF/ICSI became insignificant. IVF/ICSI patients and those of lower socioeconomic class were less likely to perform either test, whereas Christians were more likely to perform either test compared with Moslems.
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Discussion |
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The prevention of genetic diseases through prenatal diagnosis depends to a large extent on the awareness and acceptance of available diagnostic methods by the public which are in turn related to social and geographic variables. Although the triple screen test does not carry any risks to the pregnancy and amniocentesis is associated with infrequent complications, many women are reluctant to perform these tests. It is therefore crucial to evaluate the extent of utilization of these services by certain population groups and to determine the reasons for declining these tests by some women.
Data on the attitude of women who have conceived through IVF towards prenatal diagnosis is scarce. The bioethicist Cohen (1996) suggested that infertile couples do not give adequate consideration to genetic risks because of their desperation to have a child. In the present study, there was a significant difference in the rate of acceptance of prenatal diagnostic testing between women who conceived through IVF/ICSI and those who conceived spontaneously. IVF/ICSI patients were less likely to opt for prenatal diagnosis using triple screen test or amniocentesis even after controlling for confounding variables. Only 41.7% of IVF/ICSI patients did the triple test compared with 62.5% of those with spontaneous pregnancy while only 29.5% of IVF/ICSI patients of age 35 years had an amniocentesis performed. This is in contrast to the study by Elimian et al. (2003) who found no significant difference in the acceptance rate of genetic amniocentesis between women with IVF and spontaneously conceived pregnancies whether singletons (70.7 and 77.9%, P = 0.14), multiple gestations (71.1 and 62.9%, P = 0.41) or overall (70.9 and 77.6%, P = 0.07). In their study, the odds ratio for accepting amniocentesis in IVF patients was 0.84, 95% confidence interval (0.55–1.30). They suggested that women who conceived by IVF were just as concerned about having a karyotypically normal pregnancy as they were concerned about the potential for amniocentesis-related fetal loss. On the other hand, Schover et al. (1998) in an interview-based study done on 55 women starting IVF cycles reported that although 82% of couples intended to use prenatal screening by maternal blood test, only 47% planned to use invasive testing by amniocentesis or chorionic villus sampling. Respectively, the uptake of triple test and amniocentesis/CVS was 91 and 68% for maternal age 35 years, 86 and 43% for severe male factor infertility, 86 and 38% for other genetic risk factors and 67 and 28% for those with no genetic risk factors. Despite education on these risks, 71% of couples in their study had no interest in receiving formal genetic counseling. Socioeconomic status and whether the infertility factor was male or female were not predictors of a couple’s attitudes; however, Roman Catholic couples tended to have more conservative attitudes about pregnancy termination. Concerns about the cost of genetic testing and about insurance coverage were voiced by a number of couples. Schover et al. (1998) concluded that even the very small risk of miscarriage inherent in invasive prenatal testing can be a deterrent once a precious IVF pregnancy is established. In our study, only 41.7% of IVF/ICSI patients did the triple test while only 29.5% of IVF/ICSI patients of advanced maternal age had an amniocentesis performed. The rate of utilization of both diagnostic tests combined was independent of the cause of infertility although couples suffering from male infertility opted more often for triple screen test while those with female factor chose amniocentesis more frequently. The difference between our study and that of Schover et al. (1998) is that women included in the latter study were non-pregnant attempting IVF. In a pre-IVF interview, it seems likely that couples would have perceived that they needed to supply a ‘right’ answer to these questions. Previous research (Wertz et al., 1992; Adam et al., 1993; Evans et al., 1993) also suggests that fewer couples use prenatal diagnosis or actually choose to terminate an affected pregnancy than those who indicated they intended to do so when surveyed ahead of time. The motivation for prenatal testing was typically for reassurance, and pregnancy termination was anticipated to be unlikely unless a genetic abnormality would impose a very burdensome condition. However, couples who intended to use prenatal diagnostic testing were also more willing to consider pregnancy termination.
The most commonly quoted reason for declining prenatal diagnosis in both IVF/ICSI and spontaneous pregnancies was anxiety. As expected, IVF/ICSI patients more commonly cited anxiety as a reason for declining prenatal diagnosis than patients with spontaneous pregnancies. When, after years of infertility and infertility treatments, a couple finally achieves a pregnancy, one might expect that they will experience more psychological problems during the pregnancy than couples who did not experience fertility problems (Eugster and Vingerhoets, 1999). Concerning specific pregnancy-related anxiety in the mothers, IVF mothers significantly differ from the control mothers concerning their anxiety about the well-being of their unborn babies and about damage to the babies during childbirth (McMahon et al., 1997).
Studies from various countries have analyzed factors that affect attitudes of women towards prenatal diagnosis. Variables that significantly increased the utilization of prenatal diagnostic tests were non-members of a church (Tymstra et al., 1991), a higher level of maternal education (Corchia et al., 1995), white women compared with African–American women (Kuppermann et al., 1996), nulliparity, giving birth in a private hospital (Halliday et al., 1995) and urban residence (Halliday et al., 1995; Mavrou et al., 1998). In our study and after controlling for confounding variables, factors that significantly increased the utilization of prenatal diagnosis with triple screening test or amniocentesis were private insurance and Christian religion while factors that decreased their utilization were IVF/ICSI and Moslem religion.
Patients who are undergoing IVF and have reservations on prenatal diagnostic tests may be given the option of PGD. Many people see aborting a fetus as ‘killing’, whereas in the case of PGD the spare embryos are ‘allowed to die’. PGD was suggested as a more acceptable option since the decision to implant a healthy embryo coincides with the establishment of pregnancy (Cameron and Williamson, 2003). Chamayou et al. (1998) reported that the attitude towards PGD in women undergoing IVF was very positive (96% were ready to undergo PGD for aneuploidy). It was comparable, if not higher, than those with previous experience of, and those who are at risk of, conceiving a child with a single-gene defect. Katz et al. (2002) using a structured questionnaire found PGD to be a highly acceptable treatment among couples at risk of single-gene disorders, those at risk of aneuploidy and those with no genetic risks who are undergoing their first IVF cycle. On the other hand, Alsulaiman and Hewison (2006) reported that only 27% of couples with a previously affected child would accept only PGD and 13% would accept only prenatal diagnosis, while 10% would accept either technology; a total acceptance rate of only 50%. The reasons cited for refusal were ‘precious’ pregnancy, risk of multiple pregnancies, chance of mistakes and chance of not getting pregnant.
We believe that the findings of this study constitute useful information for counseling purposes, particularly for providers who may assume that women with IVF pregnancies would be totally uninterested in prenatal diagnosis. The attitude to pregnancy, prenatal diagnosis and possible termination of pregnancy might be very different for other countries depending on the religious and cultural background. As health professionals, we must continue to offer guidance to couples and make sure they have the clearest understanding of genetic risks to their offspring. Parents’ concerns are complex, and the acceptability of different reproductive technologies must be established on an individual basis. Future research should focus on methods of genetic counseling that can help couples anticipate more accurately their risk for having a child with a genetic abnormality and their emotional reaction to such a child.
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Submitted on February 19, 2008; resubmitted on June 29, 2008; accepted on July 3, 2008.
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