Embryo Transfer: Natural Cycle or Substituted Cycle?

Within the in vitro fertilization (IVF) process, the final step is embryo transfer, which in many cases is performed as a frozen embryo transfer (FET) to the mother’s uterus, where implantation will take place. The current trend toward embryo vitrification makes this step a critical point in the treatment.

For embryo implantation to occur, we need a receptive endometrium, and there are two different protocols to prepare it:

1. Substituted or artificial cycle: sequential administration of exogenous estrogen and progesterone is required.
2. Natural cycle, with its variant modified natural cycle: the natural cycle is monitored by observing selection of the dominant follicle and measuring its growth, as well as the increase in endometrial thickness. The FET is performed after spontaneous ovulation or hCG-triggered ovulation.

It is important to emphasize that there are NO differences in terms of effectiveness.

1. Embryo transfer in a natural cycle

This type of preparation should only be indicated for patients with normal ovarian function.

Follicular phase monitoring is performed, with an ultrasound around day 10 of the cycle to assess endometrial thickness and pattern, as well as serial LH measurements in blood or urine. The FET is performed 6 days after the LH surge.

In the modified natural cycle, it is more convenient because LH does not need to be monitored: an hCG dose is administered when the follicle is >16 mm to trigger ovulation, and the FET is performed 7 days later.

Advantages of endometrial preparation in a natural cycle

• Does not require exogenous hormones. A good option for patients who poorly tolerate estrogen or progesterone.
• Lower cost.
• Avoids medicalization of the first trimester of pregnancy.

Disadvantages of endometrial preparation in a natural cycle

• Cycle monitoring can sometimes be difficult for clinicians.
• Increased likelihood of cancellation due to premature ovulation.
• Requires greater flexibility from the patient for scheduling ultrasounds and planning the FET.

2. Embryo transfer in a pharmacologically substituted cycle

Indicated for patients with irregular cycles, anovulation, or absent ovarian function. However, it is the most commonly used protocol in most centers regardless of the patient’s ovarian function.

It requires sequential administration of exogenous estrogen and progesterone, which is generally well tolerated, involves little financial outlay for patients, and allows better scheduling for both clinicians and patients.

Process for the pharmacologically substituted cycle:

1. Begin after menstruation.
2. After 12 days of estrogen supplementation, perform an initial assessment of endometrial thickness and morphology.
3. If adequate, add progesterone for approximately 5 days and then perform the FET.

Advantages of the substituted cycle

• A universal protocol that is easy for clinicians to follow.
• Its main advantage is flexibility, allowing the lab and the patient to schedule the FET according to their needs.

Disadvantages of the substituted cycle

• Higher cost.
• Requires continuing treatment until 12 weeks’ gestation.
• Possible adverse drug reactions.
• An increased risk of hypertensive disorders of pregnancy has been described.

Do you have any questions or need more information?

At Fertility Madrid, we specialise in treatments such as egg donation, in vitro fertilisation and artificial insemination, among others.

Please do not hesitate to contact our professionals at our fertility clinic and they will answer all your questions without obligation.