Single or Double Embryo Transfer for Infertility

An Evaluation of Registry Data From Over 22 000 Treatment Cycles

Background: Single embryo transfer (SET) is considered the most effective method for reducing multiple pregnancies in assisted reproduction. Nevertheless, couples in Germany often opt for double embryo transfer (DET) in the hope of achieving a higher success rate. The aim of this study was to evaluate the effectiveness of two consecutive SETs compared to one DET.

Methods: We conducted a retrospective analysis of data from 133 German fertility clinics. Treatment cycles between January 2017 and December 2022 were analyzed. The parameters examined were the clinical pregnancy rate (CPR) and the live birth rate (LBR), the type of birth (single or multiple), the number of children born, the percentage of premature births, and birth weight.

Results: The rates of clinical pregnancy and live birth after fresh transfer were higher after DET than after SET (49.2% vs. 45.1% and 38.4% vs. 35.2%, respectively), but more women achieved a live birth with two SETs than with one DET (5111 of 11 205 [45.6%] vs. 4304 of 11 205 [38.4%] after DET). The number of children born per 1000 women was higher after DET (503) than after two cycles of SET (464), but DET resulted in significantly more multiple births (30.3% vs. 1.7%), fewer singleton births (26.8% vs. 37.4%), more premature births (46.5% vs. 18.1%), lower birth weight (2924.8 ± 756.8 g vs. 3264.4 ± 487.0), and significantly more very premature births.

Conclusion: Two consecutive SETs lower the risks associated with DET with a comparable success rate in terms of the number of babies born.

Cite this as: Krüssel JS, Kimmel M, Czeromin U, Blumenauer V, Bartnitzky S, Sänger N, Fehr D, Grewe C, Kupka MS, Tauchert S, Aust H, Tandler-Schneider A: Single or double embryo transfer for infertility: An evaluation of registry data from over 22 000 treatment cycles. Dtsch Arztebl Int 2026; 123: 263–9. DOI: 10.3238/arztebl.m2026.0025

Over the past decades, assisted reproductive technologies (ART) have seen a worldwide increase in use. However, ART is associated with an increased risk of a multiple pregnancy, which is a major concern. According to data from the German In-vitro Fertilization (IVF) Registry (D·I·R), this risk ranged between 12% and 19% during the period analyzed (1) and is primarily due to the common practice of transferring more than one embryo at a time. A multiple pregnancy is associated with an increased risk for both the mother and her baby/babies (2, 3). Premature birth is one of the major complications in multiple pregnancies. Premature babies are at higher risk of requiring intensive care and of developing long-term developmental disorders (3).

Many couples underestimate the likelihood of a multiple pregnancy and the associated risk of complications during pregnancy, at birth, and during the postnatal period (4). Among these couples, it is a commonly held belief that transferring multiple embryos significantly increases their chances of achieving pregnancy. A couple having two embryos available on the day of transfer must decide whether to transfer both embryos (Double Embryo Transfer [DET]) or only one embryo (Single Embryo Transfer [SET]) while the other embryo is cryopreserved for later use. Notably, the pregnancy success rates and miscarriage rates associated with the transfer of frozen-thawed embryos and with fresh transfer are comparable (1). However, the mean birth weight of full-term infants born after frozen-thawed embryo transfer was about 230 g higher than that of infants born at full term after fresh embryo transfer (5). In addition, children born after cryopreservation are more likely to have a birth weight above the 90^th percentile (large-for-gestational-age [LGA] birthweight; OR 1.48, 95% confidence interval: [1.18, 1.84]), and there is a greater risk of maternal hypertension in pregnancy (OR 1.47 [1.19; 1.81]) (6). However, artificial cycle embryo transfer, a hormonal support protocol commonly used in the past, appears to have, at least partly, been responsible for these effects, which can be reduced by applying a modified transfer strategy—a modified natural cycle with endogenous corpus luteum (7). However, cryopreservation entails additional costs of approximately 750 euros, which can deter some couples, in particular if they believe that DET offers better outcomes. Should the couple later decide not to proceed with the transfer of the cryopreserved embryo—for example, due to a change in personal circumstances—the embryo can either be donated to another woman for transfer or destroyed. To address these issues, the German Medical Association called for legal regulation of embryo donation already in 2020 (8).

The internationally established recommendation of the European Society of Human Reproduction and Embryology (ESHRE) regarding SET (9) may need to be assessed differently in Germany, where the approach differs due to the German Embryo Protection Act (ESchG). Thus, the aim of this study was to evaluate the effectiveness of two sequential SETs compared to one DET based on data from the German IVF Registry (D·I·R), which prospectively collects data from over 97% of the reproductive medicine centers in Germany.

Methods

We performed a retrospective analysis of data from 133 German fertility clinics, including treatment cycles of patients who had their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) between 1 January 2017 and 31 December 2022. Births were recorded up to 31 December 2023. Propensity score matching (PSM) was performed to minimize the impact of potential confounding factors, resulting in increased homogeneity, as evidenced by lower standard deviations (Figure 1). A more detailed description of the methods used is provided in the eMethods section.

Figure 1

Standardized mean difference (SMD) of variables before (blue triangle) and after Propensity Score Matching (orange circle)

Results

Prior to propensity score matching, a total of 25 780 treatment cycles were available for analysis. The approach of two sequential SETs was chosen in slightly over half of the cases (55.3%), while a DET was performed in 44.7% of the cycles.

After PSM, a total of 22 410 women (11 205 women in each group) were included in the statistical analysis. Before PSM, minor differences between the two treatment groups were noted. After PSM, the uneven distribution was balanced out (Figure 1; complete data analysis before and after PSM in eTable 1). Key baseline characteristics of the two patient groups are summarized in Table 1.

Table 1

Baseline characteristics after Propensity Score Matching

eTable 1

Comparison of the clinically relevant parameters in the study groups before and after propensity score matching

An overview of the findings is presented in Figure 2. After fresh-cycle DET, a total of 5632 children were born, compared to 5196 children in the SET+SET group (p<0.001; Pearson’s Chi-squared test with Yate’s continuity correction). Based on 1000 women treated, this corresponds to 503 live births after DET and 464 after a repeated SET. As expected, the clinical pregnancy rate (CPR) and the live birth rate (LBR) were higher in the DET group compared to the rates after the first SET (fresh cycle). The CPR was 49.2% [48.3; 50.1] after DET compared to 45.1% [44.1; 46.0] after SET. The LBR was 38.4% [37.5; 39.3] after DET compared to 35.2% [34.3%; 36.1%] after SET. Women who chose SET had the option of having a second SET performed. If, for the second SET, one considers only the women who did not give birth after the first SET (n = 7264), out of these 5115 received the second SET of the cryopreserved embryo. In this group, the CPR was 32.0% [30.7; 33.3] and the LBR was 22.9% [21.7; 24.0]. Of the 11 205 women in each group, 4304 (38.4%) achieved a live birth after DET and 5111 (45.6%) after repeated SET (p<0.001; Pearson’s Chi-squared test with Yate’s continuity correction). It should, however, be noted that of the 7264 women who had not given birth after their first SET at the time of the analysis, 2149 had not yet made use of the second cryopreserved embryo for a further transfer.

Figure 2

Flowchart of the groups of women who opted for either a single double-embryo transfer or two sequential single-embryo transfers. For the second SET, only women were evaluated who did not give birth after the first SET

We found a significantly higher rate of multiple births after DET compared to SET. Multiple births occurred in 30.3% of cases after DET, that is, about 20 times more frequently compared to after the first SET in the fresh cycle (1.5%) and about 15 times more frequently than after the second SET in the frozen embryo transfer cycle (2.2%). Specifically, 1281 sets of twins and 22 sets of triplets as well as one set of quadruplets were observed after DET. In contrast, both the first SET and the second SET resulted only in twin births (cumulative total of 85 cases [1.7%]). In the DET group, the probability of a singleton birth was significantly lower at 26.8% (3000 singletons/11 205 women) compared to after two sequential SETs (37.4%; 4196 singletons/11 205 women; p<0.001, Pearson’s Chi-squared test with Yate’s continuity correction).

Women who chose one DET instead of two SETs were at significantly higher risk of premature birth (46.5% [45.2; 47.8] versus 18.1% [17.1; 19.2]; Figure 3a). In addition, children born after DET had a lower mean birth weight (2.924 g [2.905; 2.945] versus 3.264 g [3.251; 3.278]; p<0,001; Welch’s t-test; Figure 3b). In the DET group, 2619 of the 5632 children (46.5%) were born before 37 weeks’ gestation and thus considered premature; in der SET + SET group, the number was about 2.8 times lower (942 of 5196 children; 18.1%). After DET, 984 children were born prematurely prior to 34 weeks’ gestation; this was approximately 3.7 times as many as the number born following a repeated SET (256 children). After DET, the number of extremely premature infants born before 29 weeks’ gestation was 213, which is more than 3.2 times higher than the 66 extremely premature infants born after two cycles of SET (Table 2; eTable 2 provides comprehensive information, including separate presentation by first fresh SET and second frozen-thawed SET). Based on all births resulting from the respective transfer strategy, the proportion of premature multiple gestation infants following DET (36.7%; 2066 out of 5632) is more than 13 times higher than following SET + SET (2.7%; 138 out of 5196). The proportion of premature singletons was 9.8% (553/5632) in the DET group and 15.5% (804/5196) in the SET+SET group (804/5 196). Figure 3c provides a detailed breakdown of the proportions of extremely premature, premature and late premature births based on weeks’ gestation, by the chosen embryo transfer option.

Figure 3a-b

Means with 95% confidence intervals for a) Percentage of premature births before 37 weeks‘ gestation; b) Birth weight in gram (g)

Figure 3c

Means with 95% confidence intervals for c) a detailed breakdown of the proportion of premature births by weeks’ gestation (extremely premature birth [<29 WG]; early premature birth [<34 WG]; late premature birth [<37 SSW]), by embryo transfer option chosen

Table 2

Analysis of children born by gestational age at birth and birth weights

eTable 2

Complete analysis of children born, by weeks‘ gestation at birth and birth weights, including separate presentation by first (fresh) SET and second (frozen-thawed) SET

Discussion

In the DET group, the number of live births was lower compared to that in the group with two SETs (4304 and 5111, respectively). The mean birth weight of children after DET was 2924.8 g [2905.0; 2.944.6], which was lower than in the group that had undergone two SETs (3264.4 g [3251.2; 3277.6]. The rate of premature births after DET was 46.5% [45.2; 47.8], which is about 2.5 times higher than the rate after two SETs (18.1% [17.1; 19.2]). Thus, the findings of our retrospective analysis of data from the 133 evaluable fertility clinics in Germany show that two sequential SETs significantly increase the likelihood of a singleton birth compared to one DET. The risk of multiple births and their complications is therefore reduced. The D·I·R data set does not contain explicit information on complications experienced by the mother or child that could lead to premature birth, such as fetal growth restriction, preterm labor or premature rupture of membranes, or that result from premature birth, such as fetal immaturity or intraventricular hemorrhage. Nevertheless, the analysis of birth weights and gestational ages provides indirect evidence of the likelihood of postnatal impairments in infants. eTable 3 provides information on the mode of birth (caesarean section versus vaginal birth) and eTable 4 information on the incidence of intrauterine fetal death. CPR and LBR per fresh IVF cycle are lower for SET compared to DET; a difference that cannot be fully offset even by an additional frozen-thawed SET—the number of live births per 1000 women is 503 after DET and 464 after repeated SET. However, this quantitative difference of 3.9 percentage points is compensated for by the significantly reduced risk of premature birth after SET.

eTable 3

Delivery mode analysis for vaginal birth and caesarian section

eTable 4

Analysis of intrauterine fetal death by weeks’ gestation

In reproductive medicine, the transfer of multiple embryos—in particular DET—has traditionally been preferred as a way to raise the chances of pregnancy and live birth. However, this strategy is associated with an increased risk of a multiple pregnancy, which, in turn, is associated with a higher rate of maternal and neonatal complications (11). These complications include:

• Preeclampsia (13.6% versus 6.4%)
• Early premature rupture of the membranes (12.0% versus 2.5%)
• Cesarean section (60.7% versus 27.4%)
• Premature birth <37 weeks of gestation (46.7% versus 7.2%), and
• Low birth weight <2500 g (38.8% versus 4.6%) (11).

Multiple pregnancy is the most important risk factor for premature birth in Germany (12). Although deaths related to multiple pregnancy after assisted reproduction are rare, they still occur more frequently with multiple pregnancies than with singleton pregnancies (13). The risks associated with multiple pregnancy increase the likelihood of long-term health complications for both mother and child and thus also place a burden on health care systems. In countries such as Sweden and Finland, where SET is increasingly being used in ART, this approach has been shown to significantly reduce the risk of premature birth. In Sweden, the rate of premature births was 23% for the period 1988–1992, compared to 13% for the period 2003–2007; in Finland, the rate was 26% for 1988–1992, compared to 18% for 2003–2007 (14). Furthermore, a reduction in long-term health consequences, such as cerebral palsy, is noted (OR DET versus SET 1.27 [1.19; 1.36]) (15). Our analysis revealed that multiple pregnancies and multiple live births occurred approximately 15 times more frequently in the DET group compared to the group of women who had opted for SET (DET: 1281 twin births, 22 triplet births and 1 quadruplet birth; two sequential SETs: 85 twin births, 0 triplet births, 0 quadruplet births) (Table 2). With only 1.6% of multiple pregnancies in the SET+SET group, this rate is comparable to that after spontaneous conception (16).

The main argument against using SET is the concern that this strategy may reduce the chances of pregnancy compared to DET, consequently lowering the likelihood of having a baby (17). Our data refuted this concern: After two sequential SETs, significantly more women achieved a live birth (5111 out of 11 205 [45.6%]) compared to after one DET (4304 out of 11 205 [38.4%]). Most probably, not all of the women in the SET+SET group who have not yet had the second embryo transferred will actually have this transfer performed. Nevertheless, additional births are expected in this group. These findings are consistent with those of previously published randomized controlled trials (RCTs), meta-analyses of RCTs and retrospective studies, and show that two sequential SETs are at least as effective as one DET (18, 19, 20, 21, 22, 23). For example, a 2020 Cochrane meta-analysis found that the rates of live births and clinical pregnancies after one SET in the fresh cycle where lower than after one DET. However, the rates of live births and clinical pregnancies after two sequential SETs and after one DET were not different and a significant reduction in the rate of multiple pregnancies was achieved with two sequent SETs. It should be noted though that most of the evidence from RCTs pertains to younger women with favorable prognoses, and that the data are heterogeneous, e.g., with regard to the developmental stages of the transferred embryos (transfers at days 2–5) (18). A key strength of our study lies in the use of prospectively collected data from the D·I·R and in the use of propensity score matching to eliminate potential confounding factors. These data realistically reflect the state of clinical care in Germany. In contrast to large clinical studies with narrow inclusion and exclusion criteria, registry data allow for the inclusion of a broader range of patients who are often otherwise unaccounted for. On the other hand, analyzing registry data carries some potential risks, such as incomplete or selective data collection. Yet, these risks are greatly reduced as a result of the comprehensive national coverage of the registry and the fact that the data fields analyzed were marked as “mandatory fields”.

One reason to decide against two sequential SETs would be that a second transfer cycle involving hormonal stimulation might be necessary, which the couple could find distressing. In the frozen embryo transfer cycle, however, most cases either do not require hormonal stimulation at all or at most require only ovulation induction which is usually well tolerated by patients. Mental and physical side effects are thus minimized compared to an ovarian stimulation cycle with oocyte retrieval (7). Multiple pregnancies and the associated perinatal complications could be significantly reduced by amending the law to also allow elective single embryo transfer (eSET) and by introducing a reimbursement structure focused on achieving the most favorable treatment outcomes. Rather than imposing mandatory SET requirements, we, as authors, advocate for education, scientific evidence and objective reasoning in order to promote SET. There is evidence that greater awareness of the associated health risks increases the preference for SET, especially when the experiences shared by other couples are taken into account (26).

Despite the robust study design, there are certain limitations to consider. While a large number of cases were analyzed and adjustments for several relevant confounding factors were made, the retrospective design of the registry data analysis still entails some risk of bias. Examples include a potentially incomplete or selective data collection or discrepancies in data collection practices used by individual centers. Furthermore, our study does not allow for definitive conclusions to be drawn about the actual complications noted in mothers or their children.

In summary, the findings of our analysis confirm the view that DET is associated with safety risks and that SET dramatically reduces these risks without adversely affecting the birth rate or the success of the fertility treatment.

Acknowledgement

We would like to thank Dr. Maren Klug, KW MEDIPOINT (Cologne, Germany), for her support in preparing the manuscript (financially supported by funds of D·I·R e.V.).

Funding

This study was funded by the German IVF Registry (D·I·R).

Conflict of interest

MK is the Head of the Administrative Office and Data Management Department of the German IVF Registry. The remaining authors declare no conflict of interest.

Manuscript received on 10 August 2025; revised version accepted on 10 February 2026

Translated from the original German by Ralf Thoene, M.D.

Corresponding author
Prof. Dr. Jan-Steffen Krüssel

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