Overview

Medical technology has developed a number of ways to bring the woman's egg and the man's sperm together outside the woman's body. A Latin phrase, in vitro, meaning "in glass," is often used to distinguish these methods from the natural method of fertilization.

When a sperm fertilizes the egg, the resulting embryo may continue to develop into a baby. The popular press often refers to children conceived through in vitro fertilization techniques as "test tube babies."

This issue brief describes in vitro fertilization and other related methods of assisted reproductive technology (ART). Specifically, it focuses on in vitro fertilization involving a couple unable to conceive a child through natural means. However, there are other methods of becoming a parent which this brief does not address. These include surrogacy, donated sperm and/or eggs, and adoption.

The topic of in vitro fertilization was chosen by HTAC because of general interest for more information about these procedures, their costs, and their effectiveness. Some aspects of in vitro fertilization are controversial and have raised medical, ethical, and legal questions. These questions are currently under debate by health care providers, payers, policy-makers and researchers as well as the general public.

Infertility

Couples who consider in vitro fertilization (IVF) have been diagnosed as infertile. Infertility is defined as the inability to conceive a child or carry a pregnancy that results in a live birth after one year of trying.¹ Infertility is generally estimated at 15% of the reproductive age population. However, IVF is used by less than 2% of those seeking treatment for infertility.

Physician office visits for infertility services have increased dramatically since 1968. In the U.S., there were 600,000 visits in 1968 and 1.35 million visits in 1988. Visits for 1995 are projected at 1.8 million.³ This increase reflects many factors-a higher incidence of sexually transmitted disease which can cause infertility, less embarrassment about seeking treatment for infertility, and acceptance that infertility can be a male or female problem. In addition, many couples are postponing marriage or childbearing until they are in their mid-30s when the chances of conceiving a child begin to decline.

Less than half of the couples who seek treatment for infertility have a child using fertility drugs, surgery to unblock fallopian tubes, or artificial insemination.⁴ When these conventional treatments do not work or are not practical, a couple may turn to reproductive physicians working with laboratory scientists who specialize in in vitro fertilization (IVF).

Natural Fertilization Versus In Vitro Fertilization

The first child in the United States conceived in vitro was born in 1981. Although IVF was originally developed as an alternative to surgery to correct for blocked fallopian tubes in women,⁶ rapid technological advances in the last five years have extended the scope of IVF treatment to infertile men.⁷ Some of these advances are summarized in the section on in vitro fertilization with micromanipulation.

To understand how IVF works, the basic steps in an IVF treatment cycle are best compared to natural fertilization.

In Vitro Fertilization with Micromanipulation

Although standard IVF offers hope to many infertile couples, it is not the answer for all types of infertility. Micromanipulation techniques called ICSI (Intracytoplasmic Sperm Injection) and assisted zona hatching, described below, are used for these difficult cases.

In Vitro Fertilization in Minnesota

There are four IVF clinics in Minnesota: three in the Twin Cities area and one in Rochester.

Three of the four clinics contacted for information reported that office visits have steadily increased since mid-1995 as the availability of ICSI has increased. Over 500 IVF treatments were performed in the three Twin Cities clinics in 1995.¹⁷ In 1996, there were over 700 IVF procedures in those clinics.^18,19,20 In one Minnesota clinic, IVF with ICSI procedures increased from 25 in 1995 to 270 in 1996.

Outcomes of In Vitro Fertilization

While natural pregnancy and child birth carry risks, IVF raises a number of additional concerns. The frequency of complications, miscarriage or birth defects associated with IVF is a matter of controversy. However, some studies have reported that these events are no more common after IVF than in the general population.^15,21 In addition, a recent study found that ICSI does not cause more birth defects or miscarriages than standard IVF.²² No long-term studies have been conducted on babies born as a result of the ICSI technique. Consequently, the long-term effects of ICSI are unknown at this time.

However, the transfer of multiple embryos in IVF procedures causes approximately 38% of all IVF pregnancies to result in multiple births (e.g., twins or triplets). Nationally, twin births constitute approximately 2% of all births. Multiple births are associated with a number of risks to the health of both mothers and their babies such as preterm birth, low birth weight, long-term disability and early death.

In February, 1997, the Centers for Disease Control and Prevention (CDC) reported that the risk of low birthweight is seven times higher among twins than for single births. Twins account for 17% of all low birthweight infants, and 12% of all infant deaths. The report added that fertility drugs and treatments, including IVF, have been associated with the 30 percent increase in twin births in the United States during 1980-1994.

ICSI and other in vitro procedures can result in a variety of medical risks to a woman's health. In about 10% of IVF procedures the use of hormones to induce ovulation can lead to a condition called ovarian hyperstimulation syndrome. Mild cases of ovarian hyperstimulation syndrome may cause the ovaries to become swollen and painful. Fluid may accumulate in the abdominal cavity and chest, the woman may feel bloated, nauseous, and experience vomiting or lack of appetite.^25,29 Severe ovarian hyperstimulation syndrome, which occurs in less that 1% of cases, can lead to stroke, kidney failure or heart attack due to too much fluid in the body. In very rare cases, vaginal hemorrhage can occur during egg retrieval.

Success Rates

To measure the success of an IVF procedure, clinics often report delivery rate, which is defined as the number of live births divided by the number of egg retrievals. However, a number of details are not available. These include: how many cycles of IVF were necessary to achieve a live birth; whether frozen embryos were used; whether a micromanipulation was employed in addition to standard IVF; or, how many pregnancies resulted in multiple births.

The American Society of Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) compile success-rate data they receive from over 300 member clinics. The data are unstandardized, self-reported and unaudited. ASRM/SART provides an overall delivery rate as well as separate statistics based on the woman's age and whether male factor infertility is involved. In 1994, the overall delivery rate for 23,050 retrievals was 21.2%. Women over 40 have a much lower delivery rate (9.0%) than women under 40.31 Fertility is negligible after the age of 45.

Some clinics report that they are able to help over 45% of the couples seeking infertility treatment by using IVF with ICSI and assisted zona hatching.¹⁸ One Minnesota clinic reports that the 1995 delivery rate for 218 retrievals was 42.2%.

Another factor that affects success rates is estrogen levels. The elevated estrogen levels produced from hormone treatments during IVF cause the uterine lining to mature at a different rate than it would naturally. This may reduce the woman's chance of becoming pregnant with each successive IVF cycle.^32,27 Clinics offer to transfer frozen embryos in order to reduce the number of hormone treatments, as well as the laboratory procedures, necessary for each new cycle.³³ (See cryopreservation above.)

Costs

A standard cycle of IVF, including $200-$3000 in drugs, costs between $8,000-$10,000.³⁴ A couple generally goes through three cycles before they have a baby or decide that IVF will not work for them. B Thus, for the average couple who may or may not conceive, costs range from $24,000-$30,000. However, if costs are considered along with the probability of becoming pregnant with each cycle of IVF (estimated at 21.2%-45%), the cumulative costs of delivering a baby are much higher. For example, costs for three cycles of IVF range between $47,667 to $132,463 per live birth.

Most clinics do not charge extra for assisted hatching. However, an ICSI procedure adds about $700-$900 per cycle. If a frozen embryo is used for a second or third cycle, the charge may be reduced to $2000 per cycle because the procedure only involves a 10-20 minute embryo transfer.

A few clinics, including one in Minnesota, will provide a partial money back guarantee, also called a "warranty" for couples seeking in vitro fertilization. For example, a couple pays a fee up front. If the woman does not become pregnant after three cycles of treatment, the clinic returns a portion of the fee.

Insurance Coverage

Relatively few insurers cover IVF because it is not considered a "medically necessary" treatment. Although being a parent may be desirable from a social or personal standpoint, IVF is not considered preventive medicine and it does not maintain health. While IVF can help a couple to become pregnant, it does not cure the condition of infertility.

Coverage of IVF is inconsistent across Minnesota health plans. While a number of health plan companies do not cover IVF, one plan offers an IVF premium package that employers or groups, but not individuals, may purchase in addition to the standard coverage package.

Since 1987, Massachusetts has mandated that insurers cover all infertility services including IVF. Ten other states have mandates which cover all or some infertility services.^36,37 Minnesota has no state mandate.

Supporters of insurance coverage for IVF services assert that if IVF procedures were used earlier in infertility treatment many less-effective procedures would not be used. As a result, the length of treatment would be shorter, and costs of infertility treatment would be lower.^38,39 One research study estimates the additional cost to a typical employer health plan would range between $2.79 and $13.95 per employee per year, depending on the level of utilization of IVF.

Access to IVF services is also a concern. For example, should lifestyle, socio-economic and/or marital status, age, medical condition or other criteria be taken into account when deciding who should receive IVF?

Without health plan coverage, IVF is available only to those with adequate personal finances to pay for the treatment. Additional questions arise, however, if health plans are required to cover IVF. For example, is coverage of assisted reproduction the best use of health care dollars given the high expenses of IVF? Should resources be focused instead on conditions or diseases that are life-threatening or lead to permanent disability?⁴¹ If coverage of IVF is required of state-regulated health plans, should coverage be extended to Minnesota's public health care programs (e.g. MinnesotaCare, Medicaid)?

Oversight of Assisted Reproductive Technology

IVF is a $350 million a year business that is largely exempt from government regulation.^32,42 However discussion concerning greater oversight of the infertility industry has grown as the technology has advanced. The ASRM/SART has moved its publication of updated ethical guidelines from 1998 to May, 1997 to address the changes in infertility treatment and assisted reproduction that have occurred since its most recent report in 1994.

The Centers for Disease Control and Prevention (CDC) is currently implementing the Fertility Clinic Success Rate Certification Act of 1992.⁴⁴ In collaboration with ASRM/SART and RESOLVE, the CDC's Assisted Reproduction Technology and Epidemiology Unit will publish an annual report of fertility clinic success rates. A goal of the process is to provide data collection and reporting that is consumer oriented and addresses the information needs of consumers. The report, slated for publication in summer of 1997, will include clinic-specific pregnancy success rates as well as data variables such as the age and diagnosis of couples undergoing IVF, number of ART initiations, oocyte retrievals, and embryo transfers.

Implementation of the 1992 Federal Act includes development by the CDC's Laboratory Practice Standards Branch of the Division of Laboratory Systems, of a model program for certification of embryo laboratories. The model is being developed in collaboration with ASRM/SART, the College of American Pathologists (CAP), and with the assistance of a variety of provider and professional groups, state and federal agencies. The model will include standards for qualifications and training of personnel, quality assurance measures, equipment maintenance, and record keeping.

Under the law states are encouraged, but not required, to implement the model either as a state activity or through accreditation by organizations such as the CAP.

It is expected that the model will be made available for public comment in the Federal Register before the end of 1997.

In October, 1995, the National Advisory Board on Ethics in Reproduction (NABER) held a conference to consider legal and ethical concerns surrounding ART, and whether increased oversight or regulation is necessary. The conference was held, in part, in response to a number of allegations of improprieties at fertility clinics in California.

In its report, NABER stated that the professional standards set by ASRM/SART and CAP are high, and that the best clinics follow those standards. NABER concluded, however, that more oversight of IVF and ART is needed and that it should be formed out of broad-based public input. Its discussion of oversight in the industry included the following:

• Additional protection may be necessary for consumers in areas such as clinic advertising, and ownership of eggs, sperm, and embryos, as well as in informed consent procedures.
• The current voluntary system lacks "teeth" by which to guarantee compliance with guidelines. In addition, there are currently no prohibitions against practices "that may be morally objectionable or collectively dangerous, such as some aspects of human embryo cloning and twinning, creation of hybrids, and a commercial market in gametes."

Arguments against greater oversight of IVF providers were also discussed by NABER. They include a concern that further regulation of already expensive ART procedures may drive the cost even higher. In addition, greater oversight may not ensure quality and adherence to ethical standards. Finally, any laws or regulations, without penalties imposed, may not prevent misconduct or irresponsible practices in IVF clinics.

Summary

IVF is not a cure for infertility. However, it does offer an opportunity for some infertile couples to have children. As a result, demand for IVF services is increasing.

This brief is intended to provide a starting point, or introduction, to IVF and related procedures as well as some of the legal, ethical, regulatory, and coverage issues. Discussion and debate has centered around concerns such as the health risks of IVF to mothers and babies, whether insurers should or should not cover IVF procedures, and the possible regulation of clinics that perform IVF. As this discussion proceeds, there will continue to be a need for reliable, objective information to help frame the debate.