ASRM/SART Clinical Guidelines

SART has developed guidelines with the ASRM for essentially all aspects the clinical practice of ART. It behooves all practitioners of ART to be familiar with these guidelines and to practice according to them. This will ensure that their patients are fully informed about their choices and that physicians will be providing ART care with the highest possible quality. Additionally, failure to follow some of the guidelines (e.g. advertising) places programs at risk of losing their membership in SART.

WHICH COUPLE SHOULD UNDERGO ART?

The question as to which couple should undergo ART is a complex one that requires appropriate evaluation of the patient’s history, physical and prior treatment. This must be combined with an understanding of the desires of the couple. Cost-benefit analysis of all the options available to each couple should then be carried. This involves identifying all the options, namely no treatment, standard infertility investigation and treatment, ART, use of donor gametes or host uterus, adoption or child-free living. Different couples will have different levels of acceptance of these various options. Some may be entirely unacceptable. It is only through careful history-taking and listening to the patient that the physician can know the answers to these questions. The value to the patient must be combined with the probability that the desired option can be achieved. It is physicians’ responsibility to inform patients of their chances for success given their unique situation. For any benefit to occur, the couple must want the outcome which is derived from the option and the probability of success must be greater than zero.

The benefit of any choice must then be balanced against the costs of the possible options. There are four generic costs. The first is financial, which is influenced by the actual dollar cost, the insurance coverage, the couple’s financial resources and their desire to spend their money on infertility care. The second cost is time-related, having to do with the patient’s age, the duration of time to obtain results from the intended choice and the amount of time the couple must commit to pursuing the option. The third cost is the health-related costs, such side effects and complications of treatment. The largest cost is usually that of high-order multiple pregnancies with ART procedures. The last cost is the emotional or psychological cost of pursuing the different options. Infertility is a life crisis for many infertile couples. Methods to deal with the stress include self-education from the media and internet, questions to the physician and staff, support from Resolve, and individual counseling when indicated.

After considering a cost-benefit analysis of the different choices, the patient should be reasonably prepared to choose which option, including ART, might be appropriate. Some specific factors should be considered when deciding which couple should proceed to ART. These include the patient’s age. ART has the advantage of achieving pregnancy more quickly than most other approaches to family building. Patients who are less than 30 may have good chances for pregnancy without ART, and more standard therapies, including “watchful waiting” after appropriate investigation, should be considered. However, patients who are older than 35 should consider ART sooner than those who are younger because their fecundity is decreasing rapidly. However, ART success rates also decrease with age, from a baseline at age 31 about 3% per year to age 34, 8% per year to age 39 and 15% per year to age 42, after which the prognosis is extremely limited. Therefore, as patients pass age 40 they need to give serious consideration to the use of donor oocytes or other options to start their families.

A second factor is diagnosis. Some conditions, such as severe tubal disease, severe endometriosis or severe male factor are almost always better managed immediately with IVF than other treatments. Data suggest that patients who have severe or extensive endometriosis have lower pregnancy rates at IVF, and this may be due to reduced ovarian response to stimulation as a result of disease and operations affecting the ovaries. As noted above, hydrosalpinges are probably associated with reduced pregnancy rates. Patients who have only one ovary also have a reduced prognosis. Sperm abnormalities can almost always be normalized through the use of ICSI. But patients with mild endometriosis, or oligo-ovulation or minor sperm abnormalities often conceive without ART procedures, and indeed can have second or third pregnancies as a result of diagnosis and treatment of an underlying disease state which can be corrected. This avoids the costs of ART and the limits the potential for high-order multiple pregnancies.

A third factor is prior treatment. Patients who have failed standard treatments of surgery, ovarian stimulation and intrauterine stimulation, and male factor treatment should proceed to ART rather than persist longer than is appropriate with ineffective standard treatments. Second surgeries are not indicated very often, and ovarian stimulation with clomiphene citrate and gonadotropins for more than 3 to 6 cycles of each is almost never indicated.

A fourth factor is duration of infertility. Patients who have not conceived after 3 to 4 years, regardless of age, diagnosis or treatment, are usually better treated by ART unless no attempt at diagnosis and treatment have been attempted in the past. It should be noted, however, that increasing duration of infertility is associated with reduced ART pregnancy rates, the odds ratio being 1.24 at one year, 0.92 at four years, and 0.66 at 13 years, regardless of other confounding factors.

A fifth factor is prior pregnancy history. Patients who have been pregnant have a higher success rate with IVF, the odds ratios for a live birth in a patient having a prior IVF live birth being 2.14, IVF pregnancy not resulting in a live birth 1.35, live birth excluding IVF 1.26 and pregnancy not resulting in live birth excluding IVF pregnancy 1.12.

Another factor to consider is the number of previous IVF attempts. A study by the SART Research Committee showed that delivery rates for the first IVF cycle was 23.4%, the second cycle 25.9 %, the third cycle 16.1%, the fourth cycle 21.0% and for greater than four cycles 15.4%. A summary of the literature data show that the second cycle has a success rate 92.7% that of the first, the third 91.5%, the fourth 87.0% and for more than four 83.6%. Therefore, for properly selected patients who can respond to ovarian stimulation medication, multiple IVF attempts can be justified on the basis of reasonable ongoing chances for success.

Finally, importantly, the decision regarding ART must also take into account other factors that can affect success. These include medical conditions and lifestyle choices such as cigarette smoking, caffeine use, alcohol and illicit drugs, weight, diet and exercise which can impact the success rate. Frank discussions and appropriate responses by the patient are always indicated in deciding which patients should pursue ART.

SUMMARY

ART is a powerful new technology that has had a profound impact on infertility care in the past two decades. The technological advances continue at an almost unbelievable rate. These scientific advances create opportunities for patients but also difficult clinical situations because the most appropriate utilization of these new technologies is not always obvious, and the chance for harming the patient is always present. It is incumbent on all physicians practicing ART to know when to proceed to ART, which procedure to use, how to have an exemplary program and how to use sound clinical judgment in helping patients decide whether or not ART is a good choice for them.

REFERENCES

  1. Callahan TL, Hall JE, Ettner SL, Christiansen CL, Greene MF, Crowley WF. The economic impact of multiple gestation pregnancies and the contribution of assisted reproduction techniques to their incidence. N Engl J Med 1994;331:224-09.
  2. Centers for Disease Control, website for 1996 CDC/SART Clinical-specific report.www.cdc.gov/nccdphp/drh/art96.htm
  3. Hu Y, Maxson WS, Hoffman DI, Ory SJ, Eager S, Dupre J, Lu C. Maximizing pregnancy rates and limiting higher-order multiple conceptions by determining the optimal number of embryos to transfer based on quality. Fertil Steril 1998:69:650-7.
  4. Meldrum DR, Silverberg KM, Bustillo M, Stokes L. Success rate with repeated cycles of in vitro fertilization-embryo transfer. Fertil Steril 1998:69:1005-9
  5. Silverberg KM, Hill GA. Reproductive Surgery versus assisted reproductive technologies: selecting the correct alternative. J Gynecol Surg 1991; 7:67
  6. Templeton A, Morris JK, Parslow W. Factors that affect outcome of in vitro fertilisation treatment. Lancet 1996; 348:1402-6. 

 

Table I

1996 SART PREGNANCY RATES PER NUMBER OF EMBRYOS TRANSFERRED

# embryos transferred Live Birth Rate Per

Transfer (Fresh, <35)

Singleton Live Birth Rate Per Transfer Multiple Live Birth Rate Per Transfer
One 9.1% 9.1% 0%
Two 20.3% 16.2% 4.1%
Three 35.8% 21.2% 14.6%
Four 36.7% 20.5% 16.2%
Five 34.4% 19.2% 15.2%
Six 36.9% 19.1% 17.8%
Seven 31.8% 16.2% 15.6%

Table II

PROPORTION OF MULTIPLE BIRTHS CORRELATED WITH LIVE BIRTH RATE

 

Total
Live Birth Rate
 

Singleton
 

Twin
 

Triplet
 

Quadruplet
Scenario A  

30%
 

59%
 

33%
 

7%
 

1%
Scenario B  

50%
 

40%
 

45%
 

12%
 

3%

Table III

NUMBER OF MULTIPLE BIRTHS CORRELATED WITH LIVE BIRTH RATE

 

Number of Patient Cycles
 

Number of Live Births
 

Singleton
 

Twin
 

Triplet
 

Quadruplet
Scenario A

Cycle 1

Cycle 2

100

70

17.6

12.4

10.0
7.0
2.1

1.4

0.3

0.2

Total

170 30.0 17.0 3.5 0.5
Scenario B 100 20.0 22.5 6.0 1.5

 

Table IV

COSTS OF PERINATAL CARE PER BABY AND PER PREGNANCY

 

Singleton
 

Twin
 

Triplet
 

Quadruplet
Per Baby  

$10,000
$20,000 $40,000 $80,000
Per Pregnancy  

$10,000
$40,000 $120,000 $320,000

Table V

COSTS OF PERINATAL CARE

 

 
Number of
IVF Cycles
 

Number of Live Births
 

Singleton
 

Twin
 

Triplet
 

Quadruplet
 

Total Cost
Scenario A $1,360,000 $300,000 $680,000 $420,000 $160,000 $2,920,000
Scenario B $800,000 $200,000 $900,000 $720,000 $480,000 $3,100,000

Assume one cycle of ART costs $8,000