OPTS - The Organization of Parents Through Surrogacy

ABSTRACT: HIGH PREGNANCY RATES WITH IVF SURROGACY
by: A. Jacobson. L. Weckstein, D. Galen, K. Hampton, K. Ivani
Reproductive Science Center of the Bay Area Fertility & Gynecology Medical Group, Inc.,
San Ramon, California 94583

The need for utilization of IVF Surrogacy is well-established. The intended mother may have an absent or defective uterus, repeated failure with regular IVF, or have a medical contraindication to a pregnancy. Our program has offered IVF Surrogacy utilizing both the intended mother's egg or donor eggs if the initial option is not feasible. The following is a report of our experience from 1995 through June 1997 with fresh embryo transfer.

Oocytes were obtained following down regulation with GnRH agonist followed by Follicle Stimulating Hormone for follicular stimulation. Surrogates were down regulated then stimulated with oral estradiol. Luteal support was achieved with both intramuscular and vaginal progesterone. Generally 3 to 4 embryos were transferred.

There were 12 IVF Surrogate Cases utilizing the intended mother's own eggs. The average age of the intended mothers was 36 years. The average age of the surrogates was 38 years. The imDlantation rate was 31%. The clinical pregnancy and delivery rates was 83%.

There were 12 IVF Surrogate Cases using egg donor. The average age of the intended mothers was 44 years. The average age of the egg donors was 27 years. The average age of the surrogates was 33 years. The implantation rate was 23%. The clinical pregnancy and delivery rate was 67% (2 surrogates in the 3rd Trimester).

In 22 Cases the partner of intended mother provided the sperm. In 2 cases donor sperm was used. In 3 cases ICSI was used. There were 1 delivered triplet pregnancy and 4 delivered twin pregnancies. All patients had embryo transfers and those who achieved a clinical pregnancy delivered at least one viable baby.

Overall the 75% delivery rate per transfer demonstrates the potential efficiency of human reproduction.

HIGH PREGNANCY RATES WITH IVF SURROGACY

INTRODUCTION

The need for utilization of IVF surrogacy is well-established. Limited case reports have attested to its success. The initial successful report was by Utian1 in 1985. The intended mother may have an absent or defective uterus, repeated failure with regular IVF, in spite of producing good embryos, or having a medical contraindication to pregnancy. Occasionally in addition the intended mother may not be able to produce eggs because of absent ovaries, a genetic abnormality, poor ovarian reserve, or a medical contra-indication to the IVF procedure. Our program, The Reproductive Science Center of the Bay Area Fertility and Gynecology Medical Group, Inc. in San Ramon, has offered IVF surrogacy utilizing both the intended mother or donor eggs if the initial option is not feasible. The following is a report of our experience from January 1995 through June 1997 using fresh embryo transfers.

MATERIALS AND METHODS

All couples, oocyte donors and IVF surrogates had a full medical and psychological screening. Follicular stimulation with follicle stimulation hormone was carried out after giving the oocyte provider depot leuprolide in the luteal phase and after down regulation was confirmed and coordination with the surrogate occurred. Transvaginal follicular aspiration was carried out 36 hours following the midcycle human chorionic gonadotropin injection.

The surrogate cycle was coordinated by using daily leuprolide injections starting in the luteal phase and then following menses using increasing doses of oral estradiol, generally starting at 2-4 ma. per day and then increasing to 6-8 ma. per day at the end of the follicular phase. The surrogate was then started on progesterone in oil 50 ma. IM and micronized progesterone capsules 200 ma. three times a day vaginally starting on the day of egg retrieval. The surrogate was also continued with 4 ma. of oral Estradiol a day. Embryo transfer was carried out either 48 or 72 hours following the egg retrieval.

All pregnancies were confirmed by sonogram and deliveries by direct contact with the surrogates and the intended mothers.

RESULTS

For IVF surrogacy with intended mother's own eggs the results are shown in Table 1. Six woman had either an absent uterus or a sign)ficant uterine problem; four had failed multiple IVF cycles; two had medical contraindications. Five women had relatives for their surrogates; two had Jacobson et al good friends. Of the 49 embryos transferred, 15 implanted and 13 babies delivered successfully. Donor sperm was used in two cases (one azoospermia; one muscular dystrophy). ICSI was used in one case. In Case B-S only one fair quality embryo was transferred. In Case DS, one of the two unsuccessful cases, only one good quality embryo was transferred. In Case BN., the other unsuccessful case the surrogate had a chemical pregnancy. The patient had her remaining frozen embryos transferred to herself which resulted only in another chemical pregnancy. All surrogates developed a good endometrium. All embryo transfers were routine except for case P-M which nevertheless resulted in a delivered twin pregnancy. One of the eight successful cases who had frozen embryos has attempted a frozen embryo transfer cycle which was unsuccessful.

For IVF surrogacy with egg donation the results are shown in Table 2. In six cases there was an absent uterus and ovaries necessitating both an ovum donor and a surrogate. Three cases involved two sisters with muscular dystrophy which will be described in detail later in this paper. The remaining three cases have a variety of reasons for this treatment. None of the oocyte donors or surrogates were relatives of the intended parents. In one case V-A-P both the oocyte donor and the surrogate were friends of the intended mother. Of the 56 embryos transferred, 13 implanted and 11 babies delivered successfully. ICSI was used in two cases, both successful pregnancies. All unsuccessful cycles were subsequently followed by a successful cycle. In one case, K-G-O by a delivered triplet pregnancy, which auto-reduced from a quadruplet pregnancy. In cases K-G-S and K-G-A, of the nine embryos transferred, only three were fair quality embryos and none were good quality embryos. In C-A-D only one good and two fair quality embryos were transferred. The first case of L-R-W in which two good quality embryos were transferred along with three fair and one poor quality embryo, the result was a chemical pregnancy. All surrogates developed a good endometrium and all embryo transfers were routine except for C-A-S which nevertheless resulted in a successful pregnancy. None of the f~ve successful cases who had frozen embryos has attempted a frozen embryo transfer cycle.

Table 3 shows the summary data for IVF surrogacy with the intended mother's own eggs and with donor eggs. There were 12 cases with the intended mother's own eggs and 12 cases with donor eggs. All intended mothers whose surrogate achieved a clinical pregnancy their surrogate delivered at least one viable baby. There were no birth defects or neonatal losses. Overall there was one delivered triplet pregnancy and four delivered twin pregnancies.

Two sisters with scapulohumeral muscular dystrophy had extraordinary experiences. Both sisters in their initial cycles used oocyte donors and surrogates, because at the time of their procedure there was no prenatal diagnosis available and because their physical condition did not allow them to carry a pregnancy to term. Both cycles C-A-S and S-S-H resulted in successful deliveries. One sister tried a second cycle with the same donor (case C-A-D) which was unsuccessful. Subsequent methodologies evolved allowing the possibility of prenatal diagnosis by chorionic villous biopsy by a program in the Netherlands. The patient underwent another cycle with her own eggs (case C-S) a five embryo transfer including one good embryo resulted in a twin

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Jacobson et
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pregnancy in the surrogate. A chorionic villous biopsy was carried out locally with the tissue being frozen and shipped to the Netherlands. Tests there revealed one normal baby and one affected baby which was subsequently aborted. A single, healthy infant was subsequently delivered at 35 weeks gestation. To the best of our knowledge this was the first prenatal diagnosis which this type of scapulohumeral muscular dystrophy.

DISCUSSION

The high success rate of 75% in 24 surrogate cases utilizing both donor and intended mother's eggs with fresh embryo transfers was gratifying. Marrs2 previously reported a 22% clinical pregnancy rate in fresh embryo transfers using intended mothers' own eggs. The difference in rates is probably partly the result of our intended mothers' younger mean age.

The higher success rates with surrogates compared with our own IVF program or even our own oocyte donor program can be partly ascribed to embryo transfers to a parous uterus unburdened by gonadotropin stimulation. The most important indicator of success was the quality of the embryos. Now that most of our embryo transfers are carried out three days following egg recovery, we are recommending insertion of only two high quality embryos in order to limit the multiple pregnancy risk. The multiple pregnancy risk with surrogacy in this series of 28% with one set of triplets is somewhat excessive.

The 24 transfer cycles represent 19 couples. Seventeen of the couples, or 89%, had a successful surrogate delivery of a total of 24 babies; one couple had two successful surrogate deliveries.

Overall the 75% delivery rate per transfer demonstrates the potential efficacy of human reproduction.

REFERENCES

1. Utian WH, Sheean L, Goldfarb JM, Kiwi R. Successful pregnancy after in vitro fertilization-embryo transfer from an infertile woman to a surrogate. N Engl J Med 1985: 313; 1351-1352.

2. Marrs RP. Gestational surrogacy - Indications, practicalities, and results. 10th Annual In Vitro Fertilization and Embryo Transfer Update. Santa Barbara, California July 1997.

Table I - IVF SURROGACY-INTENDED MOTHER'S OOCYTES

Case Patient Age Reason For Surrogacy Relation to Surrogate No. of Embryos Transferred No. of Pregnancy Sacs No. Babies Delivered

P-M 37 Multiple IVF Cycles - 3 2 2

V-C 39 Multiple IVF Cycles Sister-in-Law 3 1 1

T-D 37 Multiple IVF Cycles Sister 4 1 1

B-N 39 Multiple IVF Cycles Friend 4 0 0

M-C 32 DES Uterus - 4 1 1

B-P 40 Large Fibroids - 4 1 1

G-H 38 large Fibroids - 3 1 1

C-C 33 Asherman's Sister-in-Law 3 2 2

O-T 29 Hysterectomy Mother 3 2 2

D-S 34 Hysterectomy - 5 0 0

B-S 35 Severe Diabetes Sister 6 1 1

C-S 38 Muscular Dystrophy Friend 6 2 1

Totals 49 15 13

Table II - IVF Surrogacy Donor Oocytes

Case Donor Age Reason for Donor Reason for Surrogacy No. Embryos Transferred No. Pregnancy Sacs No. Babies Delivered

C-A-S 27 Muscular Dystrophy Muscular Dystrophy 6 1 2

C-A-D 28 Muscular Dystrophy Muscular Dystrophy 7 0 0

S-S-H 27 Muscular Dystrophy Muscular Dystrophy 4 2 1

K-G-S 22 Absent Uterus/Ovaries Absent Uterus/Ovaries 4 0 0

K-G-A 23 Absent Uterus/Ovaries Absent Uterus/Ovaries 5 0 0

K-G-O 23 Absent Uterus/Ovaries Absent Uterus/Ovaries 4 4 3

S-H-W 29 Absent Uterus/Ovaries Absent Uterus/Ovaries 4 2 2

L-R-W 26 Absent Uterus/Ovaries Absent Uterus/Ovaries 6 0 0

L-R-W 26 Absent Uterus/Ovaries Absent Uterus/Ovaries 5 1 1

V-A-P 30 Prior Poor Stimulation Prior Poor Stimulation 5 1 1

S-F-S 29 46 y/o Mother Des Uterus 4 1 1

M-S-F 29 Chronic Medical Condition Chronic Medical Condition 2 1 1

TOTALS 56 13 11

TABLE III - Pregnancy Rates With IVF Surrogacy

Source Of Ovum No. Of Cases Age Of Donor Mean Age of Surrogates Mean Implantation Rate Pregnancy Rate Per ET Delivery Rate Per ET

Intended Mother 12 36 38 31% 83% 83%

Ovum Donor 12 27 33 23% 67% 67%

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