**Author details**

prematurely. Average gestational age at delivery is estimated around 29.5 weeks for quadruplets and 29 weeks for quintuplets [17], although term delivery has also been reported, mostly as case reports [20, 134, 135]. The rates of preterm birth in the USA at <37 weeks of gestation are estimated at 96.77% for quadruplets and 100% for quintuplets and more. When it comes at <34 weeks, the estimated rates are at 93.09% for quadruplets and 100% for quintuplets [12].

Cord prolapse, hemorrhage, and abruption of the placenta are undesirable possible complications for any vaginal delivery, but in a high-order pregnancy where the mother and the fetuses are more vulnerable are even more undesirable. While there are many reviews about the mode of delivery for twin and triplet gestations, this is not possible for quadruplet and quintuplet pregnancies. For quadruplet pregnancies, vaginal delivery has been reported [136]. Cesarean section is preferred if the obstetrician is not confident enough with vaginal delivery maneuvers [137], while on the same time when an elective cesarean is selected, it allows the optimal preparation and logistic conditions [138]. The time of the elective delivery is also to be considered, with Elliot reporting choosing the 34 + 0 weeks for quadruplets [17]. Finally, further research is needed in order to safely determine whether cesarean or vaginal

The most challenging cases of quadruplet and quintuplet pregnancies are the cases where preterm labor of at least one fetus has occurred and delayed interval delivery is considered an option in order to improve the chances of survival for the remaining fetuses. Such cases with at least one newborn surviving have been published, both for quadruplet [140, 141] and for quintuplet pregnancies [142]. For twin and triplet gestations, some authors consider delayed internal delivery a viable option [143, 144], while for quadruplet and quintuplet pregnancies,

In cases of a quadruplet, quintuplet, or any high-order pregnancy, early diagnosis is crucial for the further management and treatment. The international literature concerning pregnancies with more than three fetuses is still limited, and it is not going to be any better in the future. The prevalence of high-order pregnancies after the rise until 1996 is tending to normalize, making—again—unique and rare such cases. The lack of cases and the diversity of these cases make it difficult to manage the complications, which will probably arise during a high-order pregnancy. New treatments used for singleton or twin pregnancy complications cannot always be considered as options for treating a high-order pregnancy, especially when no data are available. Beside the scientific interest for these cases and the challenge they pose to anyone dealing with them, it is always important to remember that the couple suffers the greater burden. The psychology of the couple should never be underestimated. Even by the beginning of the pregnancy, the possibility of a result not favorable is always in mind, so additional support is necessary. Fetal reduction is a method that improves the outcome of these pregnancies and could be offered as an option when there is experience with the proce-

delivery can affect the Apgar score of the newborns [139].

dure and no other limitations are present (e.g. religious).

there are still not enough data.

172 Multiple Pregnancy - New Challenges

**8. Conclusion**

Stelios Fiorentzis1 , Styliani Salta2,3, Michail Pargianas<sup>4</sup> , Artemis Pontikaki5 , Dimitrios P. Koutsoulis6 , Christodoulos Akrivis7 , Dimitrios Akrivis7 and Ioannis Kosmas7 \*

\*Address all correspondence to: kosmasioannis@gmail.com

1 Agios Nikolaos Crete, Greece

2 Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Institut National de la Santé et de la Recherche Médicale (INSERM) U938 and Institut Universitaire de Cancérologie, Faculté de Médecine, Sorbonne Université, Paris, France

3 Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France

4 Medical School, University of Ioannina, Obstetrics and Gynecology, Ioannina, Greece

5 Department of Obstetrics and Gynecology, University Hospital of Heraklion, Greece

6 General Panarcadian of Tripolis, Greece

7 Department of Obstetrics and Gynecology, Ioannina State General Hospital G. Chatzikosta, Ioannina, Greece
