Assisted fertilization

Preparation of the endometrium for embryo transfer (fresh or frozen): how does it happen?

The transfer of fresh or frozen embryos or blastocysts into the uterus is the final step of the assisted reproduction treatment started with hormonal stimulation .

The transfer takes place transcervically (i.e. through the neck of the uterus) by means of a special catheter, and can be carried out:

  • fresh , i.e. in the same stimulation cycle

or

  • using cryopreserved embryos in a previous stimulation treatment.

The fresh transfer is generally carried out on the third day from the  pick-up  (embryos with 8 blastomeres) or on the fifth day (embryos at the blastocyst stage) from the oocyte retrieval.

The transfer from frozen is programmed according to the stage in which the embryos or blastocysts were cryopreserved, and the endometrial preparation protocol used.

The treatment is successful only if the embryo (or blastocyst) takes root inside the woman’s uterus and then continues its development. This process is called implantation and depends on:

  1. the quality of the embryo
  2. by the receptivity of the endometrium .

To find out more about embryonic quality before transfer, we invite you to read this article on the classification of embryos and blastocysts .

Here, instead, we will focus on the receptivity of the endometrium and on the endometrial preparation procedures for the transfer of fresh or frozen embryos/blastocysts.

Endometrial receptivity: what does it mean?

A receptive endometrium is an endometrium favorable to implantation , i.e. ready to welcome the embryo.

This receptivity is not present on all days of the cycle, but only in a precise time interval, called the  implantation window , which is between 6 and 10 days after the LH (luteinizing hormone) peak .

In this specific period, in fact, the endometrium has some peculiar characteristics that allow the implantation of the blastocyst and one of these is given by the thickness .

What must be the thickness of the endometrium for the transfer?

The ideal endometrial thickness to favor embryo implantation is still a matter of debate. However, according to current studies, an 8mm thickness (and a trilaminar appearance ) should be achieved before starting progesterone. Below this value, the chances of pregnancy drop dramatically.

Recommendations on the number of embryos to be transferred based on the age of the woman.

Preparation of the endometrium for the transfer

Avoiding going too specific, the protocols for endometrial preparation are divided into two main groups:

  • natural cycle protocols , which do not involve the use of drugs;
  • artificial cycle protocols , which involve the use of drugs.

In both cases, the aim is to synchronize the endometrium with the age of the embryo in order to carry out the transfer at the correct moment.

Endometrial preparation protocols on natural cycle

Ovulation tracking

The woman’s menstrual cycle is monitored at set times with ultrasound to follow the growth of the endometrium and identify ovulation. Ultrasound monitoring can also be combined with biochemical monitoring to detect the LH peak and ovulation .

Ovulation stimulation

The  modified natural protocols  instead provide for the induction of ovulation  with the administration of hCG (human chorionic gonadotropin) when the dominant follicle exceeds 16 mm.

In the case of natural cycle protocols, the utility of progesterone intake is debated. If progesterone use is planned, this should be started on the evening of the LH surge.

Endometrial preparation protocols on artificial cycle

Artificial cycle protocols are generally proposed when the woman has irregular cycles or is pre-menopausal (climacteric phase).

Unlike natural protocols, they are based on the use of drugs and in particular on the administration of estrogen and progesterone .

These procedures cost more and are potentially associated with estrogen-related complications (including an increased risk of venous thrombosis, such as with birth control pills).

Ultrasound monitoring

Before starting the protocol, the patient undergoes an ultrasound check to evaluate the endometrium and exclude the presence of a maturing follicle or a  corpus luteum , conditions that would delay treatment.

Estrogen administration

The first part of the procedure involves the  administration of estrogens  (eg Progynova, Climara, etc.) orally, vaginally or transdermally (no route of administration is superior to the other).

The dosage can be fixed or gradually increased.

The task of the estrogen taken is to allow endometrial growth up to the desired thickness and at the same time  block follicular growth. 

Ultrasound monitoring makes it possible to evaluate the increase in endometrial thickness, which to be optimal must be between 9 and 14 mm and have a trilaminar appearance.

The length of time you are on estrogen can vary without interfering with implantation and pregnancy success rates.

In addition to estrogen, GnRH agonist drugs   (such as Synarel) can also be administered to prevent spontaneous ovulations. There is currently no clear evidence that the combination of estrogens and CnRH agonists increases treatment efficacy. On the other hand these drugs can reduce the number of cycles canceled. However, they are not always well tolerated by patients due to possible side effects.

Progesterone administration

When estrogens have reached their expected target and the thickness of the endometrium is considered adequate (above 8 mm), progesterone is started .

There are various formulations on the market: it can be natural or synthetic progesterone , for oral, vaginal or injectable solution (some names are Progeffick, Crinone, Pleyris, Prontogest, etc.).

When does the transfer take place after endometrial preparation?

  • In a natural cycle (NC) protocol , the LH surge is considered to be day 0 . An embryo frozen on day 3 was transferred on day 4, a blastocyst on day 6.
  • In a modified natural cycle protocol with hCG induction of ovulation (Trigger), the day of hCG administration is considered day 0.  A frozen embryo on day 3 is transferred on day 5, a blastocyst on day 7.
  • In an artificial cycling protocol, the progesterone onset day is considered day 0 (zero). An embryo frozen on day 3 was transferred on day 3 (ie after 3 days of progesterone), a blastocyst on day 5 (after 5 days of progesterone).

When does progesterone stop?

  • In fresh cycles , the progesterone is stopped after a positive pregnancy test (unless otherwise directed by your doctor).
  • In the transfer of frozen embryos or blastocysts with artificial protocols , in case of pregnancy the progesterone must be continued until the end of the first trimester as there is no corpus luteum.

When to take beta hCG after the transfer?

Each center has slightly different timings.

In general, we can say that doctors usually recommend blood sampling for beta HCG dosage 14 days after the embryo transfer on day 3 or 10 days after the blastocyst transfer .

Kathryn Barlow is an OB/GYN doctor, which is the medical specialty that deals with the care of women's reproductive health, including pregnancy and childbirth.

Obstetricians provide care to women during pregnancy, labor, and delivery, while gynecologists focus on the health of the female reproductive system, including the ovaries, uterus, vagina, and breasts. OB/GYN doctors are trained to provide medical and surgical care for a wide range of conditions related to women's reproductive health.

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