Why are we recommending single embryo transfer in our ART programs?

Cinzia Caligara, MD

Embryo Transfer

Why are we recommending SET in our ART programs? #OnlinePatientMeeting
From this video you will find out:
  • What is elective single embryo transfer?
  • Why should we prefer single embryo transfer?
  • What are the risks of multiple pregnancies?
  • Does transferring 2 embryos increase chances?
  • Can I have multiple pregnancies after a single embryo transfer?


Why single embryo transfer is recommended by fertility doctors at IVI clinic?

Dr Cinzia Caligara, gynaecologist at IVI Clinic Seville, explains why at IVI clinic doctors recommend single embryo transfer (SET) in Assisted Reproduction Treatment (ART).

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- Questions and Answers

What is elective single embryo transfer?

Elective single embryo transfer is a transfer of only one embryo when we can choose that embryo from a group of embryos. This is different when we have only one embryo, this is not elective single embryo transfer then.

Why should we prefer single embryo transfer?

Basically to avoid twin pregnancies. Nowadays, most of the clinics and also in our clinic we have very good pregnancy rates with single embryo transfer. Transferring two embryos will add around 5% higher chance of pregnancy with around 70% of the risk of twin pregnancy, and we know that the twin pregnancy has higher risk both for the babies and for the mothers. The main risk is premature labour and birth, with all the pathology associated, a higher risk of congenital malformations. For the mother, a higher risk of hypertension, premature labour, diabetes, Polyhydramnios, and the point is even if the risks of a twin pregnancy are assumable, the ultimate goal is to have a healthy baby, and a healthy mother and this is easily achieved with a single embryo transfer. We do not lose a significant amount of chances of pregnancy, so that’s why we recommend and we prefer transferring one embryo at a time. If we see the cumulative pregnancy rate so the total newborns after a cycle, we have more babies if we transfer one and then another one than if transfer two at a time.

What are the risks of multiple pregnancies?

The main is the risk is premature birth. The risk of premature birth is present even in a singleton pregnancy, this is like 1 out of 10 of the singleton pregnancies to be born before week 37. In twin pregnancies, the risk is 6 out of 10, and in triplets is 9 out of 10, and in higher-order, it’s 100%. The average time of delivery of twins is 36 weeks. If the baby is delivered before 37 weeks, there are stages of prematurity, it depends on the neurology unit care of the hospital where we are going to deliver but usually, the survival is at around 28 weeks with a high rate of complications and at about 32 weeks it’s a higher survival. The point is if patients want to have a twin pregnancy what I would suggest is to ask not only her obstetrician about the risks for twin pregnancy but also check with your paediatrician what is the advice that the paediatrician we’ll offer. Probably the obstetrician will be okay with a twin pregnancy, but for the neonatologists not, it will not be the same opinion, and the paediatrician and your neonatologists will push for a singleton pregnancy.

Does transferring 2 embryos increase chances?

Nowadays, with the blastocyst stage embryo transfer in absolute numbers it increases by about 5% and why is it not double or higher than that? Probably, because there is a lot of immunological dialogue between the endometrium and embryos that with two embryos, it increases the chance that one is compatible and the other is not. Some studies have interestingly demonstrated that if we transfer 1 good quality embryo alone, we have a higher chance of pregnancy than if we transfer 1 good embryo with 1 accompanying embryo of not so good quality. It has usually, 5% higher percentage of pregnancy but with a higher risk of twin, and if we transfer one embryo, we end up with more newborns that if we transfer the two embryos at the same time.

Can I have multiple pregnancies after a single embryo transfer?

Yes, it is possible to have twins after a single embryo transfer because of the phenomenon of the twinning of the zygote and those will be identical twins depending on how early the splitting occurs. They can have 2 placentae and 2 amniotic sacs, so just have shared the placenta with 2 amniotic sacs, or share the placenta and share amniotic sacs or be conjoined twins. The twins that share a placenta have a higher risk than the twins that have each own placenta and amniotic sac and so on. This can happen either with one embryo transfer, the incidence is low is about 1 in every 80 pregnancies, that’s about 1.5%, but it can happen also if we transfer 2 embryos and one of them can have these phenomena of twinning, so we end up with a triplet pregnancy.

Does this information also apply to transfer of 2 day-3 embryos or is this information only applicable to transferring 2 day-5 embryos?

Well, mainly to day – 5 embryos because we know that around half of the day-3 embryos don’t evolve to the blastocyst stage. So we’re speaking about the transfer.

When does the division to twins take place?

It happens very early after implantation, and it depends on the moment the embryo will divide completely and this will lead to monozygotic dichorionic diamniotic twinings, so identical twins from one embryo, one egg and one sperm with 2 placenta and 2 amniotic sacs or which is more common, only 1 placenta and 2 amniotic sacs or one placenta and one amniotic sac or the conjoined twins.

What’s the most dangerous part of freezing an embryo?

I’m not an embryologist, but I’m aware that with the new method of vitrification, it’s a very safe procedure because the problem that occurred with slow freezing that was the formation of ice meals is not present, so the risk of not surviving after vitrification is less than 5%, but I’m not an embryologist, so I don’t know if these answers the question.

Is it better to use injected progesterone?

We now, at IVI have a protocol that has been developed after excessive research that if the absorption of vaginal progesterone doesn’t reach a level of progesterone above 8 picograms per millilitres in blood, we supplement with subcutaneous progesterone, and this supplies the lack of progesterone. If the level of progesterone is above that level, it is not necessary to use injected progesterone unless the patient wants to because of the comfort of not using vaginal pessaries. In Spain we do not have oral progesterone commercialized, and now we have the subcutaneous progesterone, and we do not have a commercial form or intramuscular progesterone is a pharmaceutical firm that is made especially for the patient, it’s not commercially available.

Can I fly during my first trimester of IVF when pregnant?

Yes, there is no contraindication.

My TSH is 3.24. Is that a normal level?

That is a normal level, but when we are looking for a pregnancy, we do prefer to have the levels of TSH below 2.5. If you were a patient of mine, I would give you some medication to lower the level of TSH so that the level is 2.5. Even if 3.24 is a normal level and if you are not looking for a pregnancy, an endocrinologist will not give you treatment until the TSH of 11 or more.

I am having hot flashes and chills with night sweats what can I do? I’m 44.

I would suggest having a consultation with your gynaecologist to see your ovarian function. At 44, you can be starting the perimenopausal period, which at 44 is an early one but not an abnormal one. I would suggest having a consultation with your gynaecologist to assess your ovarian function.

Should we test the progesterone level before and after the ET? I was given 1200 of progesterone daily (3×400) and never had the progesterone tested. I just mention that after a few days of taking progesterone I was not feeling very good. What does of progesterone do you recommend to start with?

Do you test only on the day of the transfer? As I’ve mentioned, in our clinic (IVI Seville) we have a protocol of testing the progesterone at the day of the transfer and check the levels. I think more clinics are doing that, more clinicians are doing such testing, but it is like a recent addition to controlling the cycle. So I think the dosage is quite high to have a good level of progesterone. We test routinely on the day of the transfer, and if it is okay, we do not test anymore. If it is very low, we supplement with the subcutaneous progesterone in selected cases sometimes we test again after 2-3 days to make sure that the supplementation is working and we have adequate levels of progesterone. In egg donation, we start with 400 milligrams twice a day

Is it safer to have twins when doing PGD IVF for recurrent miscarriages? Compared to normal IVF?

No, it’s safer to have a single embryo transfer. I mean chromosomally euploid embryos will have a higher implantation rate. The aneuploidy is the most common cause of recurrent miscarriage, we need to minimize the impact of the immunological issues, so the recommendation in recurrent miscarriages is to avoid twins, to have a single embryo transfer. Because having twins is a risk factor for miscarriage and a patient with recurrent miscarriage doesn’t want to have another miscarriage.

Is there any study suggesting miscarriage due to COVID-19?

The scientific evidence up to today is that there is no more risk of miscarriage with COVID infection.

Do you evaluate routine antithyroid antibodies for patients with recurrent abortion?

Yes, it’s part of a diagnostic exam to tests patients with recurrent abortion.

What is the benefit of a mock cycle?

There are pros and cons. One of the pros is to be sure that the endometrium will respond properly, then we can check the progesterone in the mock cycle also and be sure if we need to supplement with progesterone or not. We also can do some studies of the endometrium, of the implantation windows and of the bacterial media of the uterus and the amount of lactobacillus. We do not routinely do a mock cycle, it depends on the patient, we personalize upon the history of the patient. The con is that you are adding one month to the treatment.

If there are only 2 day-3 embryos, is it recommended to do a day-3 transfer with both embryos or with just one embryo or leave both to try and make it to day-5 before transfer?

That will depend on the lab at your IVF centre. I can speak how it works in our clinic, we are completely sure that our lab is a safe place for the embryos and we do not perform day -3 embryo transfers, we go to day-5 in all the patients.
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Cinzia Caligara, MD

Cinzia Caligara, MD

Dr Cinzia Caligara is a Bachelor of Medicine and Surgery and Specialist in Gynecology and Obstetrics and Maternal-Fetal Medicine from the University of Costa Rica. She holds a Master’s degree in Human Reproduction from the University of Valencia, a Bachelor’s degree in Medicine and Gynaecology from the Universitá degli studi de Milano, Diploma in Methodology and Research: Design and Statistics in Health Sciences from the Autonomous University of Barcelona. Dr Cinzia Caligara has been working as a gynaecologist at IVI Sevilla since 2001. Dr Caligara has also participated in publications in magazines and has been an author of national and international book chapters.
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