Fewer Premature Births After Assisted Reproduction

Editorial to accompany the article: “Single or Double Embryo Transfer for Infertility: An Evaluation of Registry Data From Over 22 000 Treatment Cycles” by Jan-Steffen Krüssel, on the following pages

Approximately ten percent of couples seeking to conceive fail to achieve pregnancy after a year of regular sexual intercourse (1), and some of these couples then turn to reproductive medicine for help.

Here, in vitro fertilization (IVF) can be beneficial, particularly in cases of fallopian tube blockages, poor sperm quality and endometriosis (2). IVF involves retrieving eggs following hormonal stimulation and fertilizing them with the man’s sperm outside the woman’s body. The next step is to transfer one or more embryos into the uterus. Approximately 12 million children have been born worldwide using this method.

Transferring two embryos increases the likelihood of pregnancy, because both embryos have the chance to implant in the uterine lining.

A key question is how healthy children who are conceived through artificial insemination are. Premature birth plays a critical role in this regard, as it increases the risk of long-term health consequences for the children (3). Most twins are born prematurely. In Germany, the rate of multiple pregnancies after IVF is significantly higher compared to other countries. According to the most recent European statistics, the rate of twins after IVF was 16.1% in Germany in 2020, while it was 5.9% in Belgium and only 2.7% in Sweden (4).

This is due to the high rate of double embryo transfers, i.e., when two embryos are transferred to the uterus. In 2020, the rate of double embryo transfers was 57.8% in Germany compared to only 10.5% in Sweden.

The study by Krüssel et al., designed as a retrospective evaluation of registry data combined with propensity score matching, evaluated the impact of transferring one embryo or two embryos on the twin rate (5). Their analysis was based on 25 780 treatment cycles in the period 2017– 2022. Only cycles in which at least two embryos (blastocysts) were available for transfer after 5–6 days of embryo culture were included in the analysis. The first group received a transfer of two embryos. In the other group, one embryo was transferred in the so-called “fresh cycle” and, if required, a second embryo was transferred in a “frozen-thawed cycle” (transfer of a previously cryopreserved embryo). This ideal scenario where two blastocysts are available for transfer is only found in a minority of patients.

The finding that the risk of premature birth—in this study defined as a birth before 37 completed weeks of gestation—was 46.5% for double embryo transfer compared to 18.1% for two single embryo transfers comes as no surprise. Out of 4300 births following double embryo transfer (DET) and 5100 births following single embryo transfer (SET), 213 children born after DET were extremely premature (born before 29 completed weeks of gestation), compared to 66 children born after SET.

These very premature infants are at high risk of sustaining subsequent brain damage. Mothers of twins also are more likely to have complications, such as gestational hypertension and eclampsia. With no significant difference in birth rates—the ultimate goal of successful treatment—between the two groups, the long-term health consequences are of key importance.

Cultivation conditions have improved

Germany‘s current Embryo Protection Act (ESchG) is based on the conditions for in-vitro embryo culture available in the late 1980s. The “rule of three” set out in the Act only allows for the fertilization of a limited number of eggs. However, 12–18 mature oocytes should be retrieved for developing a blastocyst.

Not all of the eggs can be fertilized, and approximately 50% of the embryos die after the formation of a pronucleus (day 1 after aspiration) and up until the formation of a blastocyst (7).

Considering that embryo transfers must be highly successful given the scarcity of embryos, two embryos are often transferred at the same time in Germany. This strategy is based in the assumption that transferring two embryos in one procedure has a higher success rate compared to transferring one embryo at a time in two separate procedures. This belief is revised in the study by Krüssel et al. (5).

In other countries, however, it is legal to fertilize all eggs, thus enabling a larger number of embryos to be created to avoid the scarcity situation that leads to the decision to transfer two embryos simultaneously.

The wishes of patients are another reason why a double embryo transfer is performed. The study by Borkenhagen et al. (8) found that 81% of IVF patients did not perceive twin pregnancies as a problem. 89% viewed a twin pregnancy as desirable.

In everyday counseling practice, you often hear patients express the following wish: “We have always wanted two children, so twins would be perfectly fine.”

Many years of criticism of the Embryo Protection Act

Following the introduction of the Embryo Protection Act, it soon became clear that the restrictive approach in Germany placed a burden on all couples and on reproductive medicine, since the legislative provisions hindered the desirable goal of minimizing the risk of premature birth and, in fact, increased the likelihood of twin pregnancies.

In 2019, the German National Academy of Sciences Leopoldina called for amendments to the Embryo Protection Act and advocated that multiple embryos should be kept in culture to increase the chances of transferring a viable embryo (9). In the event that multiple embryos are available, they can generally be cryopreserved and remain available for later treatment (9). Under the law, it is also possible to donate these embryos to other women (embryo donation). Similar demands were also made by the German Medical Association in 2020 (10).

Many years of discussion on the ethics of reproductive medicine have shown that these considerations do not, in principle, constitute an obstacle to reforming the Embryo Protection Act.

The study by Krüssel et al. (5) highlights that there are practical approaches to making singleton pregnancies the goal of fertility treatment in order to prevent long-term health consequences in prematurely born children and serious pregnancy complications in the mother, such as preeclampsia. There is a need for a legal reassessment of reproductive medicine in Germany to ensure that treatment is adequate from a medical, psychological and ethical standpoint.

Conflict of interest
The author declares no conflict of interest.

Manuscript received on 13 April 2024, revised version accepted on 13 April 2026

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

Corresponding author
Prof. Dr. med. Heribert Kentenich

Cite this as:
Kentenich H: Fewer premature births after assisted reproduction. Dtsch Arztebl Int 2026; 123: 261–2. DOI: 10.3238/arztebl.m2026.0063

References

1. Boivin J, Banting L, Collins JA, Nygren KG : International estimates of infertility prevalence and treatment seeking: Potential need for infertility medical care. Human Reprod 2007: 22: 1506–12.

2. WHO, Mburu, G, Santesso N, Brignardello-Petersen R, et al.: Recommendations from the WHO guideline for the prevention, diagnosis, and treatment of infertility. Human Reprod 2026: 41: 25–38.

3. Dudenhausen JW, Maier RF: Perinatale Probleme von Mehrlingen. Dtsch Arztebl 2010: 107: 62-6 .

4. ESHRE, Smeenk J, Wyns C, et al: ART in Europe, 2020: Results generated from European registries by ESHRE. Human Reprod 2025: 40: 2038–55.

5. Krüssel JS, Kimmel M, Czeromin U, et al.: Single or double embryo transfer for infertility: An evaluation of registry data from over 22 000 treatment cycles. Dtsch Arztebl Int 2026; 123: 123: 263–9.

6. Bundesministerium für Justiz und Verbraucherschutz, Bundesamt für Justiz: Embryonenschutzgesetz vom 13. Dezember 1990 (BGBl. I S. 2746), das zuletzt durch Artikel 1 des Gesetzes vom 21. November 2011 (BGBl. I S. 2228) geändert worden ist. https://www.gesetze-im-internet.de/eschg/BJNR027460990.html (last accessed on 14 April 2026).

7. Guerif F, Le Gouge A, Giraudeau B, et al.: Limited value of morphological assessment at days 1 and 2 to predict blastocyst development potential: A prospective study based on 4042 embryos. Human Reprod 2007: 22: 1973–81.

8. Borkenhagen A, Brähler E, Kentenich H, Beutel M: Attitudes of German infertile couples towards multiple births and elective embryo transfer. Human Reprod 2007: 22: 2883–7.

9. Leopoldina: Fortpflanzungsmedizin in Deutschland - für eine zeitgemäße Gesetzgebung: Stellungnahme 2019. druckhaus köthen GmbH & Co. KG. https://doi.org/10.26164/leopoldina_03_00075 (last accessed on 15 April 2026).

10. Bundesärztekammer: Dreierregel, Eizellspende und Embryospende im Fokus—Memorandum für eine Reform des Embryonenschutzgesetzes. Dtsch Arztebl 2020. DOI: 10.3238/baek_mem_esg_2020 https://www.wbbaek.de/fileadmin/user_upload/_old-files/downloads/pdf-Ordner/MuE/2020-09-11_Memorandum_DAEB_final.pdf (last accessed on15 April 2026).