Is guided, targeted information about the risks of twin pregnancy able to increase the acceptance of single embryo transfer among IVF couples? A prospective study.

Objective To assess whether receiving information about twin pregnancy in the form of oral presentation given by a physician could affect the acceptance of single embryo transfer (SET) by couples undergoing IVF. Study design Prospective interventional study. Setting University hospital IVF unit. Patients One hundred and forty patients (70 couples) undergoing IVF. Interventions A questionnaire to measure patients’ emotions about twin pregnancy was administered to IVF patients just before and immediately after attending a slide presentation in which the risks of twin pregnancy were explained. Patients scored (1 to 6) ten adjectives linked either to positive or negative emotions; scores before and after presentation were compared. The patients’ preference between double embryo transfer (DET) and SET was also registered before and after the presentation.

The presentation about twin pregnancy caused a significant (p < 0.001) shift of the score distribution toward lower values for positive adjectives referred to twin pregnancy and higher values for negative adjectives. Information impacted similarly on women and men. Despite the relevant change in the emotional attitude, after presentation, 45.7% of women and 48.6% of men were still favorable to DET, whereas 24.3% of women and 37.1% of men preferred SET.

Oral information on the risks of twin pregnancy can affect the emotional attitude of patients toward twin pregnancy, but the wish of getting pregnant after fresh embryo transfer overcomes all rational consideration, and the majority of patients still prefer DET. Electronic supplementary material The online version of this article (10.1007/s10815-020-01820-8) contains supplementary material, which is available to authorized users.

Double embryo transfer, In vitro fertilization, Single embryo transfer, Twin pregnancy

Epidemiological data clearly shows a strong association between multiple pregnancy (including twin pregnancy) and a higher risk of maternal, fetal, and perinatal complications: the prevalence of miscarriage, pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes (GDM), intrauterine growth restriction (IUGR), cholestasis, preterm birth, cesarean delivery, postpartum hemorrhage, perinatal mortality, and pathologies affecting the central nervous system (e.g., cerebral palsy) is significantly increased in twin vs. singleton pregnancy [1–3]. In the last decades, an increasing incidence of multiple pregnancies has been registered as a consequence of the development, and spread of in vitro fertilization (IVF) [4–7] IVF-induced, iatrogenic twin pregnancies has caused huge social extra costs for obstetrical and neonatological care [8, 9]. In the last decades, reproductive medicine specialists undertook strategies aimed at lowering the incidence of twin pregnancy in IVF [10]. Several IVF programs adopted extended culture to the blastocyst stage and/or more sophisticated methods of embryo selection, like the analysis of embryo growth dynamics in time-lapse systems [11], in order to maintain acceptable cumulative pregnancy rates while performing elective single embryo transfer (eSET) [12]. In fact, eSET has been adopted by law as a standard procedure in some countries [13]. eSET is an effective tool to reduce the incidence of twin pregnancies: transferring a single embryo instead of two lowers the probability of pregnancy per transfer, but considering the good results of embryo freezing procedure, the cumulative fresh-plus-thaw pregnancy rate remains comparable to double embryo transfer (DET) strategy, while twinning rate is reduced to the minimum [14, 15]. Despite that eSET could be regarded as a simple and effective strategy to reduce twin pregnancies, it is a common experience that a significant number of infertile couples strongly favor DET [16]. Infertile couples, in fact, often start IVF programs after years of unsuccessful attempts to conceive, either spontaneously or using low-complexity treatments, and often have advanced reproductive age. Patients perceive DET as being associated with a higher and quicker success chance than eSET, and, furthermore, they frequently consider twin pregnancy as an ideal treatment outcome, allowing to get two babies at the same time, thus better fitting their family project [17, 18]. In the daily clinical practice, it is often tricky for physicians to convince patients to accept eSET instead of DET; patients’ lack scientific knowledge about obstetrical and neonatal risks linked to twin pregnancy, and this contributes to their attitude to choose a more rapidly successful, but hazardous and irrational therapeutic approach. Previous studies evaluated the impact of information on IVF patients’ attitude toward twin pregnancy and eSET; they obtained conflicting results, ranging from a mild beneficial effect [19] to the almost complete uselessness [17, 20]. In the present study, we offered a short slide presentation about twin pregnancy which was thoroughly illustrated and explained by a physician of the team to IVF couples. The aim was to determine whether receiving information about twin pregnancy in the form of oral presentation given by a physician could change the emotional attitude toward twin pregnancy and affect the acceptance of single embryo transfer (SET) by couples undergoing IVF.

A total number of 140 consecutive patients (70 couples) undergoing IVF at our IVF unit in the first 6 months of 2019 were enrolled to join the study. Patients with primary infertility, maternal age below < 43 years, very good comprehension of Italian language, and indication to IVF treatment were included. This study was approved S. Anna Hospital review board (approval number CS2/1199), and a written informed consent was given to all couples who accepted to participate in the study. Demographic and clinical data, including main cause and duration of infertility, were collected the day of controlled ovarian stimulation (COS) scheduling. Before talking with the physician in charge, the couple received a multiple-choice questionnaire that assessed the emotional attitude toward twin pregnancy (questionnaire A; see Appendices). Immediately after the completion of questionnaire A (which took 15 min), the couple attended a 10-min slide presentation (see Appendices) given by a physician of our team, illustrating the differences between single and twin pregnancies, with particular emphasis to obstetrical and neonatal risks. Immediately after presentation, the couple was asked to answer to a second questionnaire (questionnaire B; see Appendices). All data collected from questionnaires A and B were anonymously recorded in a computerized archive and treated according to Italian law 196/2003 and to the General Privacy European Regulation (EU 2016/679). Statistics Statistical analysis was performed using GraphPad Prism V7 software (GraphPad Software Inc., San Diego, CA, USA). The normality distribution of data was assessed by the Kolmogorov-Smirnov test. Continuous and categorical variables were expressed as mean ± SD and absolute/relative frequencies (percentage), respectively. To compare the replies between questionnaire A and questionnaire B, a chi-squared test for categorical variables was used. Correlation among replies to questionnaires and demographic/clinical variables was assessed by Spearman rank correlation test. Significance level was set at p < 0.05.

Demographic characteristics of the recruited patients are summarized in Table 1. Table 1. | Women (n = 70) | Men (n = 70) | | |---|---|---| | Age (years) | 36.8 ± 5 | 38.4 ± 5.4 | | Duration of infertility (years) | 3.2 ± 2.0 | | | Previous failed IVF | 1 ± 0.7 | | | Indication to IVF | || | Male (%) | 37 | | | Tubal (%) | 11 | | | Endometriosis (%) | 13 | | | Unexplained with previous failed IUI (%) | 39 | | | Married couples (%) | 71 | | | Nationality | || | Italian (%) | 83 | 89 | | Others (%) | 17 | 11 | | School level | || | Primary school (%) | 20 | 28 | | Secondary school (%) | 34 | 33 | | University graduation or doctorate (%) | 46 | 39 | | Employment | || | Steadily employed (%) | 80 | 93 | | Unemployed (%) | 20 | 7 | | Patients being twins (%) | 7 | 4 | | Patients having friends with twins (%) | 41 | 50 | The age was 36.8 ± 5 years for women and 38.4 ± 5.4 for men. This adequately reflects the average age of couples undergoing IVF in our Unit and is also in line with the average age of IVF patients in Italy. Also, the mean duration of infertility (3.2 ± 2.0 years) is close to the one generally observed in Italy, where couples undergo IVF rather late, probably because of the strong ethical and/or religious concerns about the procedure. Of note, 73% of the recruited couples had a history of one or more failed IVF cycles. Twenty-nine women (41.4%) had a positive pregnancy test with a clinical pregnancy confirmed by transvaginal ultrasound during the IVF cycle in which this survey was performed; 6 out of 29 (20.1%) were twin pregnancies. Overall, most couples (71%) were married, whereas the others, certified to steadily live together, were native Italians (83% of the women, 89% of the men), and in more than 70% of the cases, at least one of the two partners had a high scholar level (doctorate, graduation or secondary school certificate) and a steady employment (Table 1). Among patients included in the study, 7% of women and 4% of men had a twin brother or sister, whereas 41% of women and 50% of men stated to have one or more friends having twins. The self-evaluation of the knowledge about twin pregnancy is reported in Table 2. Interestingly enough, before receiving information, women claimed to be more informed than their male counterparts. A thorough assessment of the patients’ knowledge about twin pregnancy was not the aim of our study, nor was it the assessment of the couples’ learning capability. We took care to provide very simple information with minimal content of technical terms and to allow patients to receive all explanations by the physician. The slide presentation aligned the self-perceived level of knowledge within the couple, as after it, about 95% of patients (both women and men in similar proportion) improved their self-perceived consciousness about the course and outcome of twin pregnancy (Table 2). Table 2. | Women (n = 70) | Men (n = 70) | | |---|---|---| | Before attending slide presentation | || | Poor or any (%) | 23 | 56 | | Average (%) | 59 | 33 | | Good (%) | 19 | 11 | | After attending slide presentation | || | Poor or any (%) | 1 | 0 | | Average (%) | 4 | 6 | | Good (%) | 95 | 94 | All 140 patients replied to the questionnaire aimed at assessing their emotions about twin pregnancy by giving a 1-to-6 score to 10 adjectives linked either to positive (nice, merry, wonderful, joyful, happy) or negative emotion (tricky, anxiogenic, difficult, worrying, terrifying). The scoring exercise was repeated twice, just before (questionnaire A) and immediately after (questionnaire B) having attended the guided presentation explaining the characteristics of twin pregnancy compared to single pregnancy (see Appendices). The score of each adjective was considered low (1–2), medium (3–4), or high (5–6); the proportion of patients giving a low, medium, or high score was calculated for each adjective, and the distribution of patients before and after presentation was compared. Overall, scores were similar comparing the two partners of each couple, and no significant differences were found between men and women taken as groups. Before receiving information, the frequency of positive emotions related to twin pregnancy was directly and significantly related to the patients’ age (both for men and women), the duration of infertility, and the number of previously failed IVF attempts (r = 0.43, p < 0.01 at Spearman’s test). The slide presentation about twin pregnancy caused a highly significant (p < 0.001) shift of the score distribution toward lower values for positive adjectives and higher values for negative adjectives (Table 3). The given information impacted in a comparable way on women and men, and finally, only 37.7% of women and 39.7% of men still gave a high (5–6) score to positive adjectives, whereas 70.9% of women and 56.7% of men gave a high score to negative adjectives (Table 3), suggesting that a quite relevant change in the emotional attitude toward twin pregnancy had occurred. The opinion of patients being themselves twins did not differ from that of the whole group. Even patients with prior failed IVF cycles gave answers not significantly different from those given by couples at their first IVF attempt: this could be linked to the fact that previous failed cycles were just one in most cases and two in two cases. Table 3. | Before presentation | After presentation | |||||| |---|---|---|---|---|---|---|---| | Low (1–2) | Medium (3–4) | High (5–6) | Low (1–2) | Medium (3–4) | High (5–6) | p | | | (A) Women | ||||||| | Positive adjectives (%) | 11.7 | 35.4 | 52.9 | 22.6 | 39.7 | 37.7 | < 0.001 | | Negative adjectives (%) | 10.9 | 40 | 49.1 | 5.1 | 24 | 70.9 | < 0.001 | | (B) Men | ||||||| | Positive adjectives (%) | 7.7 | 32.9 | 59.4 | 20.6 | 39.7 | 39.7 | < 0.001 | | Negative adjectives (%) | 31.1 | 34.3 | 34.6 | 20 | 23.7 | 56.7 | < 0.001 | Despite the significant emotional change observed in both sexes after attending the presentation, when couples were requested to express a preference among SET, DET, or multiple embryo transfer (MET), replies were largely in favor of DET (Table 4). In fact, although patients preferring SET increased significantly (from 7.1 to 24.3% among women, from 20 to 37.1% among men), and those preferring MET decreased almost by half in both sexes, the majority of patients (45.7% of women, 48.6% of men) still indicated DET as the preferred choice, also after the presentation (Table 4). Table 4. | Before presentation | After presentation | |||||| |---|---|---|---|---|---|---|---| | SET | DET | MET | SET | DET | MET | p | | | Women (%) | 7.1 | 71.4 | 21.4 | 24.3 | 61.4 | 14.3 | < 0.001 | | Men (%) | 20 | 48.6 | 31.4 | 37.1 | 45.7 | 17.1 | < 0.001 |

It is definitely established that multiple pregnancy (including twin pregnancy) implies a significantly higher incidence of maternal, fetal, and perinatal complications, negatively affecting the most important IVF outcome, healthy live birth rate, as well as the overall cost for public health systems. Nowadays, it is mandatory that IVF specialists exert any possible effort to reduce the incidence of twin pregnancy, which has always been significantly higher after IVF than after spontaneous conception [10]. An effective strategy to reduce the incidence of twin pregnancy without significantly lowering IVF effectiveness is the extensive application of the transfer of a single, well selected embryo (eSET) [11, 12, 14]. The practice of eSET for selected groups of IVF patients has been imposed by law somewhere [13], but in most countries, it is just recommended and remains one of the possible options for both physicians and patients. As very commonly experienced by IVF doctors, it is often difficult to convince patients to accept eSET. Patients undergoing IVF may have advanced reproductive age and a long history of infertility, with several failed therapeutic attempts; they feel a very strong, and sometimes desperate, need of obtaining a pregnancy as soon as possible and perceive the transfer of more than one embryo as associated with a higher, and quicker, chance of success [21]. In countries where patients find poor or any support from the public health system in covering the relevant costs of IVF, success rate is by far prevailing over any other consideration, as a couple can afford only a very limited number of IVF attempts, sometimes just one. Moreover, some IVF patients consider twin pregnancy as an ideal outcome, perfectly fitting with their family project of having more than one child [17, 22–24]. In addition to these factors, the scarce awareness of most patients about the obstetrical and perinatal risks linked to twin pregnancy is undoubtedly one of the major factors leading to their wish of getting a double or multiple embryo transfer [25]. Previous studies investigated whether giving educational material to IVF patients in order to improve their knowledge of twin pregnancy could affect their preference about the number of embryos they would like to be transferred. Results were conflicting: some authors reported a beneficial effect of additional information on the preference of single pregnancy [24], the risk of prematurely delivering a baby with low or very low birth weight being particularly effective in orienting patients toward eSET [21, 22]. Differently, other authors reported that specific information had impact neither on the acceptability of eSET [20] nor on the wish of obtaining a twin birth [17]. The present study is the first in which IVF patients received information on twin pregnancy by means of a dedicated oral presentation given by a physician and not only simply receiving educational material for self-reading. Differently from previous studies, we could be sure that both women and men received information and that all presented data were clarified adapting to the instruction level of the couple and to their possibility to understand. Self-reading, in fact, can be skipped or can be misunderstood by non-mother language patients. Overall, we observed that (a) the self-perceived level of knowledge after receiving information increased dramatically, as patients who stated to have acquired a good knowledge of twin pregnancy increased from 10–20 to 95%; (b) information significantly reduced the prevalence of positive emotions about twin pregnancy and increased the prevalence of negative emotions; (c) information significantly increased the proportion of patients preferring SET (from 7.1 to 24.3% among women, from 20 to 37.1% among men), but those choosing DET were still the majority (45.7% of women, 48.6% of men). In conclusion, these findings show that couples thinking that transferring two or more embryos would offer them a higher chance of rapidly getting pregnant are poorly receptive to rational thinking. Actually, a quite relevant proportion of them do understand that a twin pregnancy may imply additional problems (even potentially serious problems) compared to a single pregnancy, but still, the wish of getting pregnant soon, thus finding the “happy end” of their long story, overcomes any other rational consideration. Making efforts and spending time to give the best possible information to IVF patients is not a useless loss of energy but is likely to have a limited impact on the patients’ compliance to the proposal of transferring a single embryo. Probably the best solution to further reduce the rate of multiple and twin pregnancies after IVF will be a more extensive application of laws and regulations compelling to apply eSET, at least to specific subgroups of good prognosis IVF patients. Electronic supplementary material Compliance with ethical standards This study was approved S. Anna Hospital review board (approval number CS2/1199), and a written informed consent was given to all couples who accepted to participate in the study. Footnotes Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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