What is the best embryo transfer protocol for gestational carrier frozen embryo transfers?

Between 1/1/2023 and 4/7/2025 our office has performed 23 single euploid embryo transfers to gestational carriers resulting in 16 ongoing pregnancies with a fetal heartbeat (70%). We typically expect about 93% of pregnancies with a heartbeat to go on to live birth. A 70% fetal heartbeat rate per embryo would correspond to about a 65% live birth rate per embryo ( 0.93 * 16/23 = 0.65 = 65%).

Typically for these embryo transfer cycles we use daily subcutaneous lupron to prevent ovulation and then when menses starts add estradiol by mouth 2mg three times a day. We do a TVUS 10-12 days after starting estradiol to check the endometrial thickness and appearance before adding progesterone. Our most common progesterone dosing is Prometrium (micronized progesterone) 200mg vaginally three times a day and progesterone in oil 50mg every 3 days (Prometrium PO TID and PIO Q3D). We transfer on the 6th day of progesterone administration. This protocol prevents ovulation to ensure that the pregnancy results from the transferred embryo rather than natural conception from the gestational carrier’s oocyte.

For non-gestational carrier single euploid embryo transfers we only see a 50% fetal heartbeat rate per embryo with this protocol (Prometrium PO TID and PIO Q3D), and a 63% fetal heartbeat rate with modified natural frozen euploid single embryo transfer without letrozole (Femara). This is an increase of 26%.

So does that mean that for a gestational carrier cycle we potentially could see a fetal heartbeat rate of 88% per euploid embryo with a modified natural cycle frozen single euploid embryo transfer? This would result in an expected live birth rate of 82% per single euploid embryo ( 0.93 * 0.88 = 0.82 = 82%). So we potentially could go from a 65% to a 82% live birth rate per single euploid embryo. If we wanted to design a prospective RCT to evaluate this we would need to randomize 210 embryo transfers for an 80% power at an alpha of 0.05.

Given that modified natural FET cycles also lower the rate of preeclampsia compared to non-ovulatory FETs (also called programmed or hormone replacement cycles), maybe this is already enough justification to move to modified natural FETs for gestational carriers. At the least, we should consider offering this.

The biggest challenge to modified natural FET cycles for gestational carriers is that inevitably a gestational carrier will conceive a pregnancy from the egg she ovulates during that cycle. Another possibility is that a twin pregnancy will be conceived with one fetus from the transferred embryo and the other fetus from the oocyte that the gestational carrier ovulates during the FET cycle.

Therefore, before any modified natural FET to a gestational carrier both the gestational carrier and the intended parents would need to consent to this. There would need to be coordination with the legal representation of both parties and both parties would need genetic counseling. There would need to be a plan in place for testing during the pregnancy likely with non-invasive blood testing of the gestational carrier. There would also need to be a plan for testing at birth with a cheek swab of the infant or infants after delivery.

Likely the legal documentation would need to state than any offspring conceived from the embryo transfer would belong to the intended parents and any offspring conceived from the ovulated oocyte would belong to the gestational carrier and her partner. There would also need to be some consideration for how to handle toher unanticipated situations that may arise as a result of transfer in an ovulatory cycle.

This research has been approved by the Christ Hospital IRB (protocol #25-030).