Genetic & Gestational Surrogacy Overview:
Many think surrogacy is a new technological advance but this is not necessarily correct. Genetic surrogacy (sometimes called conventional surrogacy) dates back to biblical times when Sarah was unable to bear Abraham a child, she provided him with Hagar, her maid, to bear the child for her (Genesis 16.1-4). In this example, the third party provided both the egg and the uterus and the off-spring is a genetic mix of the genetic surrogate and the male partner.

Indications for genetic (conventional) surrogacy:

• Absent or poorly functioning ovaries combined with loss of the uterus
• Maternal disease which precludes pregnancy but not motherhood
• Maternal genetic diseases

While genetic surrogacy has been around for a long time, it took mankind many years to perfect science to be able to preform In Vitro Fertilization (IVF) and gestational surrogacy. The first gestational surrogacy procedure was reported in 1985 (Utian WH, et al. Successful pregnancy after in vitro fertilization-embryo transfer from an infertile woman to a surrogate. N Engl J Med 1985;313:1351). In this particular instance, the woman's uterus had been removed but the ovaries remained in place. The couple were able to produce and egg and sperm that formed an embryo through IVF techniques. The embryo was then transferred into a host uterus of a third party for gestation and delivery. In this particular instance, the surrogate did not have a genetic investment in the pregnancy.

Indications for gestational surrogacy:

• Absent uterus
• Malformed uterus
• Recurrent pregnancy loss
• Repeated IVF implantation failures

How do we choose a surrogacy facility and what questions should we ask?
The success rates of the surrogacy procedures are entirely dependent upon the overall success rates for the given ART facility. Statistics for surrogacy procedures are available but it currently takes a minimum of two to three for the statistics to be published so they are frequently out-of-date. It is very important that the commissioning or intended couple seek detailed statistics regarding from the specific facility they are evaluating. Below are some questions that may be helpful in deciding which ART facility to use in the surrogacy process:

General questions for choosing any surrogacy or ART program:
Is the program headed by a board-certified reproductive endocrinologist?
What is the general ART experience of the practice?
What is the general reputation of the physician?
What surrogacy contract experience do the legal staff have?
Are personal statistics provided or only general publication statistics?
Is the laboratory headed by a full-time experienced Andrologist/Embryologist and is the laboratory open for your personal inspection?
Do the physicians and nurses answer your questions adequately, return your phone calls quickly and do they tend to your emotional needs?
What are the exact costs of the proposed therapy?

Questions specific for genetic (conventional) surrogacy:
What are the success rates for the various insemination procedures in the program?
What are the donor sperm pregnancy rates per cycle in the ART program?
What are the success rates for genetic surrogacy?

Questions specific for gestational surrogacy:
What are the general success rates for the IVF procedures?
What are the success rates for egg donation in this program?
What are the success rates for gestational surrogacy?
What are the frozen embryo transfer (FET) rates in this program?

Few centers in the world have significant experience in the fields of surrogacy. Large centers have the advantage of experience while smaller centers may provide more individualized attention. Price is also a factor in the decision of where to go with price ranges differing from $10,000 to $20,000 between some locations.

What are the success rates for gestational surrogacy? The latest national statistics were published in 1995 but reflect 1993 data. This publication summarized the statistics of a total of 267 ART programs. Only 58 (22%) programs offered gestational surrogacy (see Figure 1).

Figure 1: 1993 published statistical success rates for gestational surrogacy in Assisted reproductive technology in the United States and Canada: 1993 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 1995;64:13-21.

A clinical pregnancy simply means that a positive pregnancy occurs and a pregnancy sac (gestational sac) is seen in the uterus. Clinical pregnancy rates will differ with respect to the age of the women who provides the eggs and the skills of the ART program. It is not uncommon for some of the better programs to achieve a 40-60% clinical pregnancy rate per initiated cycle. Spontaneous abortions can sill occur and multiple pregnancies are reported separately (see Figure 2).

Figure 2: Final results per clinical pregnancy in gestational surrogacy in Assisted reproductive technology in the United States and Canada: 1993 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 1995;64:13-21.

The spontaneous pregnancy loss rates are dependent upon the age of the individual who provides the eggs. The pregnancy the loss rates for women 35 years old (y.o.) are 15%, 35-40 y.o. are 20%, and > 40 y.o. range from 30-40%. The actual multi-fetal pregnancy rates may also have been higher than reported since embryo reduction procedures were available to reduce triplet and quadruplet pregnancies to twins. As has been shown for many years, pregnancies that are conceived through ART are not at a greater risk of having genetic abnormalities or fetal malformations.

If enough embryos were created during the first IVF procedure, the additional embryos may have been stored in liquid nitrogen for later use. The success rates for frozen embryo transfer (FET) are generally less than those for fresh transfers but it is usually cost effective for the surrogate to still undergo a FET procedure. Some programs are getting 25% clinical pregnancy rates per FET procedure which is greater than the 13% as reported in the 1993 data (see Figure 3).

Figure 3: Frozen embryo transfer pregnancy rates in Assisted reproductive technology in the United States and Canada: 1993 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 1995;64:13-21.

How is genetic (conventional) surrogacy accomplished? In the genetic surrogacy procedure, sperm from the husband of the infertile couple is placed into the genetic surrogate. Before modern medicine, copulation was generally used to accomplish this feat. In more recent times, less scientific techniques have been used such as the "turkey baster" technique. No one really knows how successful this technique is since controlled studies are lacking. This technique may be used by lesbian women to procreate a child when copulation is not desired and medical assistance in unavailable or unwilling to assist.

There are essentially two insemination techniques currently used in genetic (conventional) surrogacy today. The first does not involve the direct input of a medical team. The sperm is collected and allowed to liquefy at room temperature for about twenty minutes and then placed in a syringe that is missing the needle. The syringe is then placed into the vagina and the sperm injected. The problem with this technique is that the timing of the placement of the sperm must first be ideal. Second, the sperm only survive about 15-30 minutes in the vagina and only the sperm that ascend into the cervix and genital tract survive. The second and more concerning problem is that the male who provided the sperm may not have been fully tested for sexually transmitted diseases. Yet another potential problem involves legal concerns which should really be fully addressed before the sperm is actually placed.

Common Sperm Preparation Techniques:

• Double-Wash
• Swim-Up
• Percoll Preparation

The second method that is more frequently used for genetic (conventional) surrogacy involves the insemination process. First, sperm is prepared through concentration techniques. The time close to ovulation is generally determined with the assistance of urinary luteinizing hormone (LH) test kits and transvaginal ultrasounds. Ovulation induction medications are generally not needed but may be used if success is not quickly achieved. The highly concentrated and purified sperm are most commonly placed into the uterus (IntraUterine Insemination or IUI) or Fallopian tubes (IntraTubal Insemination or ITI) themselves with slender catheters during a painless insemination procedure.

What are the success rates for genetic (conventional) surrogacy? The success rates of the insemination process used in gestational surrogacy procedures are not very well studied. The reason is that it is actually uncommon for normal sperm to be inseminated into a normal female patient. There is ample data available looking at insemination success rates in infertile couples but little information with normal patients.

What influences success rates for genetic (conventional) surrogacy?

• age of the genetic surrogate
• quality of the semen
• timing of the insemination process
• sperm placement location

As discussed previously, sperm is placed into the surrogate at just the right time of the month to maximize the chances for conception. When possible, it is ideal that a fresh specimen be placed. The chances for conception are statistically increased with fresh sperm compared to frozen sperm frozen sperm. (O'Donovan PA, et al. Treatment of male infertility: is it effective? Review and meta-analyses of published randomized controlled trials. Hum Reprod 1993;8:1209-22.)

Under ideal circumstances, the general chances for conception using natural intercourse in young fertile couples are estimated near 20% each month. In the genetic (conventional) surrogacy procedure, the insemination is generally performed only once that month with the statistical chances for success decreasing slightly over natural success rates.

In the genetic surrogacy process cryopreserved sperm may also be used. In this case, the success rates may be quite similar to those seen with sperm donor insemination procedures. In the donor insemination procedure, frozen sperm obtained anonymously and cryopreserved at a central laboratory. The sperm is frozen in liquid nitrogen and is eventually transported to and stored in the insemination facility itself. The sperm is thawed and prepared just prior to placement. Placement of the sperm into the cervix itself results in lower pregnancy rates so the concentrated sperm is usually injected into the uterus (IUI) or tubes (ITI) themselves.

As early as 1776, Lazzaro Spallanzani reported the effects of freezing human semen. Human sperm successfully fertilized and induced normal embryonic development in 1953 with the first successful human birth reported in the 1960's. (Bunge RG, et al. Fertilizing capacity of frozen human spermatozoa. Nature 1953;172:767.) Commercial cryobanks were developed in the 1970's and reached a heightened level of activity in the 1980's when it became essential to use cryopreserved sperm to prevent the transmission of the virus responsible for AID's. The cryopreservation process is achieved through the following process:

• 1. Collecting the specimen through masturbation
• 2. Chemically removing some of the water within the sperm themselves to prevent ice crystal formation at the time of freezing.
• 3. Supporting the sperm within a cryoprotectant buffer (often glycerol) which further prevents damage to the sperm during the freezing and thawing processes.
• 4. The sperm are then cryopreserved via a stepwise fashion in liquid nitrogen at - 196øC and stored for variable lengths of time in glass ampules, cryovials or plastic straws.
• 5. A small sample from an ejaculate may be thawed to evaluate the CryoSurvival Factor (CSF) of the thawed specimen. The goal is to have at least half of the sperm remain motile following the freeze-thaw sequence.

The length of time the sperm can remain frozen is uncertain and may easily be over 10 years with a pregnancy recently published following nearly 16 years of storage (Mortimer D. Practical Laboratory Andrology. New York: Oxford University Press, 1994:302.). This cryopreserved specimen may be transported anywhere in the world making it ideal for use in distant surrogacy facilities.

In a recent literature review, the chances for pregnancy using frozen sperm placed in the cervix yielded pregnancy rates of only 4.6% (25/538) per cycle while placement of the sperm into the uterus through the Intra-Uterine Insemination (IUI) procedure yielded three times the pregnancy rate at 14.6% (106/726) per cycle (Sweet, CS, Intra-uterine placement can increase effectiveness of donor insemination. Concepts 1992;1:1-2.) (see Figure 4).

Figure 4: Intra-Uterine placement of cryopreserved donor sperm triples the success rates compared to cervical placement of sperm. (Sweet, CS, Intra-uterine placement can increase effectiveness of donor insemination. Concepts 1992;1:1-2.)

Double insemination procedures with one performed on one day and another on the following day have also been shown to increase the chances for success. ( Byrd W, et al. A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm. Steril 1990;53:521-7.) This procedure may be quite useful when single insemination procedures have not been successful.

In summary, it is ideal that the genetic surrogate has the fresh sperm placed and if the specimen has to be cryopreserved and thawed, it is far better to place the specimen into the uterus via the IUI or ITI procedures. If success is not rapidly achieved, one can consider performing double inseminations.

What are the costs for the surrogacy procedures?
The costs of the basic procedures are quite complex and must be discussed in detail. It is the responsibility of each interested couple to ask detailed financial questions of the ART facility. Look for well documented fee schedules and estimates that strive for accuracy. It is very helpful for the facility to have some experience and to provide previously tested and realistic estimates.

It is exceedingly difficult for physicians to research fees so that comparative data is simply not easily available. Part of the problem is that the Federal Trade Commission (FTC) prohibits physicians from discussing their prices with each other. Apparently, the FTC feels that any discussion of prices could lead to price fixing. No other professional group has such rigid restrictions in place. Little research has, therefore, been performed to determine what fees are charged for similar procedures at various locations.

The fees tend to be similar in a regional since word-of-mouth eventually informs the ART practice of the prices of their competitors. Local support groups may be helpful but the patients are often informed of their own charges and not of comparative costs for all the various procedures.

The fees are generally quite higher in highly populated regions such as California and New York while the fees are frequently reduced in less populated regions. One variable that is uncertain and quite specific to the location involves legal fees and reimbursement techniques of the surrogate herself. Some states allow reimbursement for medical expenses only while other states allow for some form of re-enumeration to be given to the surrogate herself. Having skilled attorneys involved in this part of the process is essential but this type of professional assistance has its price.

Below is a list of some potential unexpected costs of the surrogacy process:

• Pregnancy complications costs
• maternal complications
• fetal complications such as multiple pregnancy complications
• Costs for uterine evacuation procedures for spontaneous pregnancy losses
• Costs for selective reduction in multi-fetal pregnancies
• Costs for genetic amniocentesis
• Costs for termination of a genetically abnormal pregnancy (rare)
• Ongoing psychologic counseling costs
• Medical complication costs (rare)

No matter how good the attorneys are, unforeseen fees and problems can occur. It is important, therefore, to choose all parties involved in the surrogacy process carefully so that adversarial relationships will not occur. It can not be emphasized enough that the couples seek written estimates from the ART facilities and attorneys and to some comparative shopping. Simply compare apples-to-apples between the various programs and try to look at their success rates since the "dollar-for-baby" fees are what are really desired.

Summary Comments: This manuscript is meant to be an overview. Nothing can replace a careful interview with the ART center that you would like to work with. Ask lost of questions and look for complete answers. Be an informed patient.