EFFECTIVENESS OF TREATMENT WITH DONOR GAMETES

Donor gametes can be exceedingly successfully used to provide an option for infertile couples. Donor sperm is used much less frequently since intracytoplasmic sperm injection has evolved to treat almost all male factor infertility. Pregnancy rate can almost be doubled by using ovarian stimulation and IUI. (Table V). Donor oocytes are used to treat poor ovarian function from whatever cause, age being the most common. Pregnancy rates with donor oocytes are much higher than those with the usual infertile population because of the improved egg quality. The age of the recipient has minimal impact on the success rates, which are 35 to 50% per cycle.

EFFECTIVENESS OF IVF AND GIFT

The effectiveness of IVF and GIFT are shown in Tables I, II, III, and V. IVF has success rates between 5 to 40%, with an average around 20% per cycle. GIFT may have a slightly higher success rate than IVF, and may be recommended in women with known normal tubal and sperm function and possibly in older women. However, it is not clear whether the apparent increase in GIFT success rates is real or due to other factors, such as patient selection. Intracytoplasmic sperm injection (ICSI) results in pregnancy rates equivalent to women with no male factor. There is only a slight reduction in the success rates with IVF with increasing numbers of cycles. An increasing duration of fertility also decreases success rates. Previous pregnancy and live birth increases success rates slightly. Most diagnostic categories have similar success rates, except that patients with multiple pelvic surgeries or history of severe endometriosis have lower success rates by about 5%. Some endometriosis patients may benefit from pre-treatment for two months with ovarian suppression.

Factors equally affecting IVF and non-IVF success rates include in utero DES exposure, adenomyosis, myomata, congenital uterine anomalies, and incompetent cervix. Higher multiple pregnancy rates with IVF may cause greater complications in patients with uterine abnormalities. Nonsurgical factors affecting all success rates include cigarettes, caffeine, alcohol, and other drugs.

AGE AND DURATION OF INFERTILITY AS A CONFOUNDING VARIABLE IN DETERMINING EFFECTIVENESS OF TREATMENT

It is well documented that female age is the single most important variable affecting outcome both with IVF and non-IVF treatments. Ovarian function declines with age, and results in her fertility at age 37 being approximately 70% of that at age 20 to 25, 55% at age 40, 30% at age 43, and 10% at age 45. Furthermore, an elevated cycle day 3 FSH and/or estradiol renders the situation even less hopeful. Nevertheless, women who have been previously fertile and who undergo tubal ligation reversals over 40 have been reported to have live birth rates approaching 50%. Hull has documented the important practical conclusions regarding age. (Table VI).

Duration of infertility has a profound impact on fecundity. A healthy, normal couple in their early twenties have a fecundity of approximately 30% the first month they attempt conception, 25% the second month, 20% the third, 15% the fourth, and then a gradually decreasing fecundity to about 8 to 10% by the end of one year. After two years of attempting, monthly fecundity is approximately 6 to 8%, at three years 4 to 6%, and four years about 2%. These fecundities are lowered further in older women and by any diagnosed infertility factor.

COSTS OF INFERTILITY TREATMENT

The cost of infertility treatment is difficult to quantify, especially when separated out from the costs of diagnosis. Some issues associated with cost have been addressed in the manuscript, "Cost Effective Fertility Diagnosis". The relative cost of some treatments and fecundity per cycle for endometriosis are shown in Table VII, and the approximated relative costs of courses of treatment in Table VIII. These tables can be utilized as rough approximations in decision-making. Costs and success rates must be individualized to each physician's circumstances and unique patient situation, but these numbers most likely reflect realistic estimates in many practice settings. It must be emphasized that the cost of pregnancy increases with more intensive care because of the adverse selection of poorer prognosis patients into these treatment groups. Additionally, more intensive and expensive treatment is generally reserved for patients who have failed to conceive on less intensive and expensive treatment.

An increasingly popular way to determine cost-effectiveness of treatment is to divide the cost of treatment by the probability of a pregnancy. This has resulted in some astounding costs (eg $212,000) in selected circumstances. Another approach is to calculate the effectiveness by the number of patients needed to be treated to gain one extra pregnancy over and above that which would have been expected without treatment. This methodology is important because it accounts for treatment-independent pregnancies. Another important cost factor of IVF and GIFT procedures is associated multiple births. It has been reported that the cost of a singleton baby is about $10,000, twin baby $19,000 (pregnancy $38,000), and triplet baby $36,000 (pregnancy $109,000). The single greatest cost of IVF may be the cost of caring for multiples. This is therefore an important clinical problem which is being addressed by limiting the number of embryos replaced among other approaches.

PREGNANCY RATES FOLLOWING TREATMENTFOR UNEXPLAINED INFERTILITY

TREATMENT	MONTHLY FECUNDITY (%)
No treatment	3
IUI	4
Clomiphene	6
Clomiphene plus IUI	18
Gonadotropin	8
Gonadotropin plus IUI	18
IVF	23
GIFT	26

Guzick, Data submitted for publication

 

 

TABLE II

PREGNANCY RATES FOLLOWING TREATMENTFOR TUBAL FACTOR INFERTILITY

TREATMENT	PREGNANCY RATE (%)
Salpingolysis/ovariolysis	25-62
Fimbrioplasty	60-70
Fimbrioplasty (post-infectious)	27
Salpingostomy (tubal reconstruction)	21-39
Tubal anastomosis	52-82
Tubal anastomosis (ureterotubal junction obstruction)	50-69
Tubal cannulation	25-35
Salpingostomy (for ectopic pregnancy)	38-80
Methotrexate (for ectopic pregnancy)	50-55
Fulguration of endometrial implants	40-75
Repeat tuboplasties	6-20
IVF (per cycle)	15-25

Adapted from Silverberg and Hill

J Gynecol Surg 1991;7:67

 

TABLE III

OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY

TREATMENT	STAGE / MONTHLY FECUNDITY (%)
	MINIMAL/MILD	MODERATE	SEVERE
Expectant	3	3	0
Medical *	3	4	2
Surgical	5	5	3
IVF (per cycle)	19	16	12
GIFT (per cycle)	34	36	20

* After discontinuation of ovarian suppression medications

TABLE V

PREGNANCY RATES FOLLOWING TREATMENT BY DONOR GAMETES

TREATMENT	MONTHLY / CYCLE FECUNDITY
Donor insemination (frozen)	9%
Ovarian stimulation plus IUI	16%
Donor oocyte IVF	35 - 50%

 

TABLE IV

BEFORE AND AFTER TREATMENT FOR DIFFERENT UTERINE ANOMALIES

	TYPE OF ANOMALY	FETAL SURVIVAL RATES
		PRE-TREATMENT (%)	POST- TREATMENT (%)
I	Segmental mhllerian agenesis or hypoplasia%	0	0 - 90
II	Unicornuate uterus%	0 - 40	40H
III	Uterus didelphys Strassman Cerclage % %	60 30 50	60H 85 90
V	Septate uterus	25	90
VI	Arcuate uterus% %	80	80H
VII	DES-exposed uterus%	65	65H

% Only some anomalies can be treated

% % Not all anomalies need to be treated

H Surgical repair, cerclage, and/or intensive antenatal care may increase the fetal survival rate

 

TABLE VI

 

1. Age effects in the man on fecundity are slight until about 55, and are linked with considerable increased genetic risks for the offspring.

 

2. Age effects in the woman on fecundity cause accelerated decline after about 37, and very sharp decline after 40, reaching virtually zero by 45.

3. The decline in female fecundity is mainly due to oocyte quality and is linked to genetic risks for the offspring.

4. The decline between 35 and 40 seems to affect mainly nulligravid rather than previously fertile women.

5. Nulligravid women should perhaps not use oral contraception after the age of 30.

6. Nulligravid women should not delay attempting to conceive beyond the age of 35, and then should pursue proper fertility investigations and proven treatment if necessary within one year at most.

7. Basic investigations of infertility should particularly include accurate diagnosis of sperm dysfunction, especially in men without obvious seminal defects, to enable confident choice of DI or other treatment before reaching an adverse age.

8. Ovarian failure and the menopause can be advanced several years by destructive ovarian surgery. Conservation should be a dominant consideration in all surgical practice, such as internal destruction of endometriotic cysts rather than excision if difficult.

9. The normal decline in oocyte quality with age is associated with reduced ovarian responsiveness to gonadotrophic stimulation, and the chance of successful treatment by any means is virtually zero when FSH levels rise above the normal limit, irrespective of age or menstrual cyclicity.

10. Ovarian responsiveness is reduced but unpredictable when the FSH level is approaching the upper normal limit. Success rates of treatment are reduced but offer realistic hope.

Hull, Pacific Coast Fertility Society

Postgraduate Course Syllabus

April 14 - 18, 1993

TABLE VII

RELATIVE COST AND FECUNDITY PER CYCLE

TREATMENT	COST	RELATIVE COST	FECUNDITY	RELATIVE FECUNDITY	COST PER PREGNANCY
OBSERVATION	$50	1.0	3%	1.0	$1,667
CLOMIPHENE +IUI	$500	10.0	7%	2.3	$7,142
GONADOTROPIN + IUI	$2,500	50.0	15%	5.0	$16,667
IVF / GIFT	$9,000	180.0	30%	10.0	$30,000
SURGERY (1 YEAR) MIN/MILD/MOD	$8,000	160.0	Min/Mild/Mod 5%	1.67	$17,391
SURGERY (1 YEAR) SEVERE/EXT	$10,000	200.0	Sev/Ext 3%	1.0	$32,258

 

From Adamson, ASRM Practice Committee, 1997

 

TABLE VIIAPPROXIMATED RELATIVE COSTS OF COURSES OF TREATMENT

TREATMENT	COST	DURATION (MOS)	TOTAL COST	APPROXIMATED ECPR	COST PER PREGNANCY
OBSERVATION	$50	12	$600	31%	$1,935
CC + IUI	$500	3	$1,500	20%	$7,500
HMG + IUI	$2,500	3	$7,500	39%	$19,230
IVF / GIFT	$9,000	3	$27,000	66%	$40,909
SURGERY Min/Mild/Mod	$8,000	12	$8,000	46%	$17,391
SURGERY Sev/Ext	$10,000	12	$10,000	31%	$32,258

From Adamson, ASRM Practice Committee, 1997

REFERENCES

1. Templeton A, Morris JK, Parslow W. Factors that affect outcome of in vitro fertilisation treatment. Lancet 1996; 348:1402-6.

2. 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.

3. Neumann PJ, Johannesson M. The willingness to pay for in vitro fertilization: a pilot study using contingent valuation. Med Care, 1994;32:686-99.

4. Bates GW, Bates SR. The economics of infertility: Developing an infertility managed-care plan. Am J Obstet Gynecol 1996;174:1200-7.

5. Rabin DS, Quadeer U, Steir VE. A cost and outcome model of fertility treatment in a managed care environment. Fertil Steril 1996;66:896-903.