Center for Infertility and Reproductive Surgery

Treatment Options

Intrauterine Insemination (IUI)

Indications:

• mild male factor
• minimal endometriosis
• unexplained infertility

Therapeutic Donor Insemination (TDI)

Indications:

• severe male factor (oligospermia or azoospermia)
• women without partners
• lesbian couples

TDI involves timed insemination from an anonymous or a known donor. Use of frozen semen to prevent sexually transmitted disease is recommended by the FDA and the CDC. At sperm banks, donors are tested for sexually transmitted diseases, including HIV, chlamydia, gonorrhea, syphilis, CMV, HTLV I and II, and hepatitis. Commercial sperm banks are the source of donor sperm in the majority of cases. Sperm banks provide information about physical characteristics, medical history, education, and ethnic or racial background of donors. More recently, some donors have given permission to sperm banks to disclose their identities if requested by the child at some point in the future. Since success rates for cycles with frozen sperm are slightly less than with fresh sperm, this treatment should be continued for three to six cycles before consideration of adding or changing therapy.

Ovulation Induction

Indications:

• ovulatory dysfunction, unknown cause
• polycystic ovary disease (PCOD)
• hyperprolactinemia
• hypothalamic amenorrhea
• premature ovarian failure

Ovulation induction is associated with a favorable prognosis. When ovulation induction is successful, pregnancy rate per cycle approaches that of normally ovulating women for age group. To determine whether estrogen secretion is adequate a progestin challenge test can be done. This involves giving a progestin (such as medroxyprogesterone acetate) 10 mg daily for five days (after making sure the pregnancy test is negative). If there is a withdrawal bleed within 14 days of stopping the progestin, there is adequate estrogen secretion. Absence of a withdrawal bleed indicates low estrogen secretion due to pituitary or hypothalamic dysfunction, or premature ovarian failure. An FSH test distinguishes between these two diagnostic categories (low or normal in hypothalamic-pituitary dysfunction; high in premature ovarian failure).

Drug	Dosage	Cost	Comments
Clomiphene citrate (Clomid™)	50 to 150 mg po qd days 5-9 of cycle	$5/pill, or $15-45 per cycle	Appropriate initial treatment for patients with unexplained infertilityor PCOD. Cervical mucous can become thick on this medication, and therefore IUI is often recommended if the patient does not conceive within three cycles. Approximately a 20-25 percent pregnancy rate per cycle. If no pregnancy after three to six cycles, other causes of infertility should be investigated. Risks include ovarian hyperstimulation syndrome (1 percent) and multiple births (5-10 percent).
Gonadotropin therapy. Human menopausal gonadotropins (HMG; e.g., Pergonal™) or purified FSH (Metrodin™, Follistim™ , or Gonal-F™)	1-2 ampules IM (administered at home by patient or partner) starting day 3 of cycle. Dose is altered depending on number of follicles and estradiol level by day 7	Pergonal™: $66.50/ 75 IU Follistim™: $85/75 IU Gonal-F™: $50/37.5 IU $88/75 IU $169/150 IU	Requires the patient to come in approximately qod starting day seven of cycle for ultrasound measurement of follicle size and estradiol levels. When the lead follicle is 18-20 mm in size and estradiol levels are 400-1500, hCG is administered IM and 12-36 hours later, timed intercourse or insemination should occur. > Success rates extremely high for patients with hypothalamic amenorrhea (over 90 percent cumulative pregnancy rates over six cycles), but slightly lower rates for patients with PCOD or unexplained infertility. Not recommended for women with premature ovarian failure due to low success rates. Complications include ovarian hyperstimulation syndrome (10-20 percent) and multiple births (25 percent, with 20 percent twins, 5 percent higher order multiple births).
Dopamine agonists (Bromocriptine or Dostinex™)	Bromocriptine: 2.5-7.5 mg po qd Dostinex 0.25-1 mg po 2x/week	Bromocriptine™: $51-154/mo. Dostinex™: $141-$562/mo.	Restores menstrual cycles in 90 percent of women with hyperprolactinemia. For women with elevated prolactin but normal menstrual cycles, bromocriptine alone is less likely to be beneficial.
Metformin (Glucophage™)	500 mg po qd	$14/mo.	Decreases insulin resistance, and in one study, when given in conjunction with clomiphene citrate, restored ovulation in 90 percent of patients.

Assisted Reproductive Therapy

	Indication	Procedure
In Vitro Fertilization (IVF)	· tubal factor · severe endometriosis · unexplained infertility · male factor	Involves controlled ovarian hyperstimulation, which is aimed at producing multiple oocytes. Once the oocytes are mature, hCG is administered and 34 to 36 hours later, they are retrieved under ultrasound guidance with the patient under light general anesthesia.The oocytes are then combined with sperm in a Petri dish to allow for fertilization.The embryos are incubated in growth medium and then transferred back into the female partner’s uterus three to five days later.
Cryoembryo Transfer	Indicated for patients who have undergone a cycle of IVF in which excess eggs were cryopreserved.	In this procedure, the excess cryopreserved fertilized embryos from the previous IVF may be transferred at a later time.The advantages of this procedure are that a repeat ovarian stimulation can be avoided. In addition, this procedure allows a woman with advanced maternal age to use embryos that were fertilized with oocytes from when she was younger.
IVF with Donor Oocytes	· premature ovarian failure · perimenopause, or   menopause · failed IVF due to oocyte   factors (comprises 50%   of cases)	The donor may either be anonymous or selected by the couple. A legal contract is needed between the donor and the recipient couple prior to initiation of the procedure. Insurers do not cover the payment to the donor and screening of the donor.
Intracyto-plasmic Sperm Injection (ICSI)	· congenital absence of   the vas deferens · obstructive and non-   obstructive azoospermia   or men with less than   one million total motile   sperm · previous vasectomy	ICSI involves direct injection of a single sperm into the cytoplasm of an oocyte. Success has been reported even with immotile and immature sperm. Success rates are the same as those reported for IVF, approximately 35% per embryo transfer.
Gestational Carrier	· women without a uterus · women with a medical   condition that preclude   carrying a pregnancy   to term · male homosexual couples	Involves IVF (see above) with transfer of the embryos to a gestational carrier, which is a woman with a uterus who will carry the pregnancy to term.To avoid custody lawsuits, when oocytes are needed, use of a separate oocyte donor, (i.e., an individual who is different from the gestational carrier) is recommended.This is particularly important for male homosexuals or for women who lack functional ovaries or uterus, or who have a medical contraindication to pregnancy. At Brigham and Women’s Hospital, surrogate carriers (women who are inseminated with the male partner’s sperm and who carry the pregnancy) are not used.