Re: progesterone level before FET transfer

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Here is my suggested/personal  approach to FET:

Two decades ago, when women went through IVF (in vitro fertilization), they usually had their embryos put in the uterus right after the eggs were collected in the same cycle (known as “Fresh” Embryo Transfer). Freezing embryos at that time was risky, with about 30% not surviving the process, and those that did had lower chances of successfully implanting and growing a healthy pregnancy compared to fresh embryos. This was because the slow freezing process led to ice forming within the embryo’s cells, harming them.

But things changed with a new, faster freezing method called vitrification. With vitrification, embryos are frozen so quickly that ice crystals don’t have a chance to form. More than 90% of embryos survive this process in excellent condition, just like they were before freezing, giving them a better chance to develop into healthy pregnancies.

Modern advancements in frozen embryo transfers (FET) have shown great promise, possibly even surpassing the success rates of transferring “fresh” embryos. This improvement likely isn’t because of the freezing process itself, but rather due to two key factors:

1. a) FET often involves transferring blastocysts that have been carefully tested and selected through preimplantation genetic screening (PGS)/preimplantation genetic testing for aneuploidy ( PGT-A) , increasing the chances of a successful pregnancy compared to “fresh” transfers where such selection is not done.
2. b) The hormone replacement therapy (HRT) used for FET helps prepare the uterus optimally for implantation, improving the overall conditions for a healthy pregnancy compared to the ovarian stimulation with fertility drugs used in Fresh IVF cycles.

Considering these factors, FET offers several clear advantages:

• Safe storage of extra embryos for future transfers.
• Flexibility to delay transfers for additional testing or to avoid complications.
• Preserving embryos for selective transfer in cases of advanced maternal age or diminished ovarian reserve (DOR).
• Convenience in assisted reproductive services involving third-party parenting, like egg donation or gestational surrogacy.

These advancements provide hope and options for couples seeking successful IVF journeys and healthy outcomes for growing families.

The advent of PGS/PGT heralded a major advance in IVF as it enables us to choose the healthiest embryos for transfer to the uterus, thereby significantly boosting the chances of a successful pregnancy. The performance of PGS/PGTA virtually mandates that advanced embryos ( blastocysts) be biopsied 5-6 days after fertilization and that an additional period of 10 days be allowed for genetic testing to be performed. It follows that such blastocysts be vitrified and stored for FET to be performed in a later cycle. 

For women who are older or have a lower number of eggs (diminished ovarian reserve-DOR ), as well as those who have faced repeated pregnancy loss or IVF failure, PGS/ PGT-A can be a game-changer. It helps identify the best embryos for successful transfer. However, for younger women who tend to have normal egg reserves, and because of their youth produce a larger number of quality eggs/ embryos the benefits of PGS might not be necessary.

When it comes to creating a reserve of embryos through “Embryo Banking,” FET is mandatory and ground-breaking. Here, multiple IVF cycles are conducted over an extended period of time allowing for the collection and banking of a good number of advanced ( usually PGS/PGT-A tested)  embryos ( blastocysts) for future dispensation. Once we’ve gathered a promising group of such embryos, well-timed FETs can be undertaken, significantly improving the chances of a successful pregnancy and reducing the risk of miscarriage.

Through these advancements, we are able to offer greater  hope and possibilities to those on their journey to parenthood, making IVF an even more effective and accessible option.

Let’s break down the process to prepare the uterus for a frozen embryo transfer (FET) in simpler terms:

• Cycle Start: To begin, the recipient takes birth control pills (like Marvelon, Desogen ,Lo-Estrin etc.,)for about 10 days. The patient commences 0.75mg Dexamethasone daily OR 10mg prednisone BID at cycle start. This is continued to the 10^th week of pregnancy (tailed off from the 8^th to 10^th week) or as soon as pregnancy is ruled out
• Hormone Kickstart: After 10 days, they start another medication called Lupron/Lucrin/decapeptyl/ Superfact/ Buserelin  through a shot.
•  Monitoring Progress: The doctors keep an eye on the progress by doing ultrasounds and blood tests to make sure things are on track.
• Boosting Hormones: Delestrogen 4mg IM is injected, twice weekly (on Tuesday and Friday), commencing within a few days of Lupron/Lucrin/Superfact, Decapeptyl-induced menstruation. Blood is drawn on Monday and Thursday for measurement of blood [E2].  This allows for planned adjustment of the E2V dosage scheduled for the next day. The objective is to achieve a plasma E2 concentration of 500-1,000pg/ml and an endometrial lining of >8mm, as assessed by ultrasound examination done after 10 days of estrogen exposure i.e., a day after the 3^rd dosage of Delestrogen.  The twice weekly, final (adjusted) dosage of E2V is continued until the 10^th week of pregnancy or until  pregnancy is discounted by blood testing or by an ultrasound examination. Dexamethasone/Prednisone is  0.75 mg is taken (as above) and oral folic acid (1 mg) is taken daily commencing with the first E2V injection and is continued throughout gestation.
• Antibiotic prophylaxis: Patients also receive Ciprofloxin 500mg BID orally starting with the initiation of Progesterone therapy and continuing for 10 days.
• Luteal support: commences on day-1 , 6 days prior to the FET, with intramuscular progesterone in oil (PIO) at an initial dose of 75-100  mg (-Day 1). Daily administration- is continued until late in  the evening of Day 5 ( I suggest 10.00PM-11.00PM) . Daily PIO (75mg-100mg) is continued until the 10^th week of pregnancy, or until a blood pregnancy test/negative ultrasound (after the 6-7^th gestational week), discounts a viable pregnancy. Also, commencing on the day following the FET, the patient inserts one (1) vaginal progesterone suppository (100 mg) in the morning  + 2mg E2V vaginal suppository (in the evening) and this is continued until the 10^th week of pregnancy or until pregnancy is discounted by blood testing or by an ultrasound examination after the 6-7^th gestational week.

• Timing the  FET: This  is performed as early as possible on the morning of Day-6
• Blood pregnancy Testing:  Blood pregnancy tests are performed 13 days and 15 days after the first PIO injection was given  

*Note: In cases where intramuscular progesterone administration is not well tolerated, we tend to use a vaginal  gel known as Crinone8%. This gel is used twice a day (morning and evening) until the day of the embryo transfer.

• Preparing for Transfer: On the morning of the embryo transfer, we pause using the gel but resume it in the evening. The day after the transfer, we continue using the gel twice a day. . If the blood pregnancy tests show a positive result and 2-3 weeks later an ultrasound examination confirms a viable pregnancy, the Crinone 8%  gel is continued twice daily up to the 10th week of pregnancy

Regime for Thawing and Transferring Cryopreserved Embryos/Blastocysts:

Patients undergoing FET with cryopreserved embryos/ blastocysts will have their embryos thawed and transferred by the following regimen.

• Monitoring Pregnancy: Regular check-ups and tests are done to confirm if the pregnancy is successful.

Geoff Sher