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In natural cycle FET, the endometrium develops under endogenous hormonal stimulation. In medicated FET estrogen pills or shots are used to prepare the endometrium for implantation. NC FET is a good option for patients who cannot take oestrogen while medicated FET allow for advance scheduling.
For infertile couples supported by IVF (In Vitro Fertilization), embryo freezing is a technique used regularly to optimize the pregnancy rate per retrieval of oocytes. The embryo (s) can then be thawed and transferred (FET) to achieve a live birth. (1) The transfer is carried out at a time when the endometrium is receptive, which is necessary for embryo implantation and pregnancy. This period is defined as the implantation window. The implantation window can also be assessed by the monitoring of a natural cycle IUI (NCI) FET. (3) The choice of the key moment for the transfer is determined by ovulation or the rise of progesterone. To date, no study has demonstrated the superiority of one protocol over another in terms of the birth rates. However, in medicated frozen embryo transfer treatment is usually carried out by daily subcutaneous injections of gonadotropins followed by ovulation induction. In this context, the implementation of the FET in natural cycle may appear less burdensome for the patient and more physiological. The development of the dominant follicle and endometrium is monitored by ultrasound and FET is timed after triggering ovulation induction or determination of the spontaneous LH (luteinizing hormone) surge. (2)
In this article we will look at
- What is natural cycle frozen embryo transfer?
- What is medicated frozen embryo transfer?
- What is the success rate of natural FET and medicted FET?
- What are the future outcomes of natural FET and medicated FET?
Natural cycle FET requires extensive preparation, timing and planning. In NC-FET planning of embryo thawing and transfer requires the identification of a period of optimal receptivity. This putative ‘window of implantation’ starts shortly after ovulation. The chances of conceiving are greater If an embryo is transferred within this window. Planning NC-FET can either be done based on recognition of the LH surge (luteinizing hormone) that precedes ovulation (using serum or urine LH monitoring) or by triggering ovulation (sometimes referred to as modified NC-FET). (4) Using modified NC-FET, the development of the dominant follicle is closely monitored by regular ultrasonic evaluation. On reaching a diameter of 16-20 mm human chorionic gonadotrophin (HCG) is administered and ovulation takes place approximately 36 h later. Embryo thawing and transferring can be planned accordingly. Despite ultrasonic monitoring, spontaneous ovulations do occur. In such an event the start of the window of implantation cannot be predicted accurately. Since the identification of the onset of the window of implantation is essential for further timing of FET, cycles with spontaneous ovulation are usually canceled. To minimize cancellation, patients are required to visit their clinic several times which can be time consuming and expensive. In natural FET cycles, 5 to 6% of all patients have insufficient development of the dominant follicle and/or endometrium thickness and treatment has to be canceled. However, a clear advantage of NC-FET is the fact that it does not require patients to take medication for several weeks. Overall, natural cycle frozen embryo transfer has the advantage of not requiring medication but this advantage is balanced against the need for frequent ultrasonic evaluation of the dominant follicle, the risk of insufficient development of the endometrium and the risk of unexpected ovulation and/or dominant follicle. Due to these factors, NC-FET is more difficult to plan. (5)
Due to the disadvantages of natural cycle frozen embryo transfer, an artificial or medicated FET has been developed. Medicated FET was originally developed for patients undergoing oocyte donation. It was also found to be successful for patients undergoing FET treatment. During medicated FET patients start with daily estrogens which are supplemented with progesterone when the endometrial thickness is considered sufficient. Patients maybe required to take these drugs for several weeks. The main advantage of medicated FET is that it requires little ultrasonic monitoring and therefore is more easily scheduled placing less burden on both patients and doctors agenda. Moreover, planning thawing and transfer is flexible and can be performed based on convenience. Some also claim that supplementing estrogen reduces cancellation rates due to insufficient endometrium thickness compared to natural cycle-FET. The main disadvantages of medicated-FET are possible side effects and a higher risk of thromboembolic events. (6)
In recent years several, retrospective, studies comparing live birth rates in both NC-FET and medicated-FET have been published. More recent studies have concluded that NC-FET results in higher pregnancy rates. However, in a retrospective analysis of 1677 FET cycles, it was observed that there was no difference in pregnancy rates between NC-FET and medicated-FET. The rates of pregnancy did not differ significantly between both groups. Current evidence does not demonstrate a significant difference in pregnancy rates between these two methods of endometrial preparation. There is no literature available discerning which regimen patients prefer, which has fewer side effects, or which is the most cost-effective. If live birth rates indeed are equal in NC-FET and medicated-FET the perceived burden of treatments, convenience and cost-efficiency might be important factors in choosing one of both options. (7)
Natural cycle-FET and medicated-FET do not differ significantly in live birth rates. The use of HCG (Human chorionic gonadotropin) in planning NC-FET remains a subject of debate. (10) In recent years both randomized prospective studies, as well as retrospective studies, have been publicized with conflicting results. In one study NC-FET based on ovulation induction was chosen after careful considerations. (9) There are several issues when using LH (luteinizing hormone) determination for timing FET. (10) Also, there is no information on whether pregnancy rates could be improved if adjustments are planned for thawing and transfer according to the presence of LH surge. No such studies have been conducted so far in patients undergoing ultrasound monitored unstimulated cycle FET. (8)
Follow OVO Fertility blog for more information on fertility treatment. Contact OVO Fertility today to find out more about natural and medicated embryo transfer programs and let us help you decide which one is right for you. Reach us at +918268260808.
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