ARTIFICIAL INSEMINATION

ARTIFICIAL INSEMINATION - Jennifer E. Cyrkler, MD; Megan E. Bower, RN, MPH
BASICS
DESCRIPTION
• Artificial insemination is the placement of washed sperm into the female reproductive tract.
• Placement can be intracervical, intrauterine, intraperitoneal, or intrafollicular.
• Most common is intrauterine insemination (IUI).
• Sperm are washed to reduce antigenicity.
• Insemination can be with partner's sperm or therapeutic insemination with donor sperm (TID).
• Fecundity is inversely related to maternal age.
• Contraindications to artificial insemination
- Infection (acute cervicitis, endometritis, acute prostatitis, epididymitis, salpingo-oophoritis)
- Anovulation
- Pregnancy
- Unexplained uterine bleeding
• System(s) affected: Endocrine/metabolic; Reproductive
• Synonym(s): Therapeutic insemination; Intrauterine insemination
EPIDEMIOLOGY
Predominant age: Reproductive-age women (18-45)
Incidence
Varies, depending on etiology of infertility
RISK FACTORS
• Male factor: 35%
• Cervical factor: 10%
• Testicular trauma from vasectomy, prostatitis, or a genetic predisposition can predispose to serum antibody production.
• Cervical trauma from cryotherapy, loop electrosurgical excision procedure, conization, or laser therapy can cause poor sperm-cervical mucous interaction.
ETIOLOGY
Indications for intrauterine insemination
• Absence of a male partner
• Male factor infertility: Oligospermia, asthenospermia, hypospadias, retrograde ejaculation, coital dysfunction
• Female factor indications include: Cervical mucous abnormalities
• Male factor with sexually transmissible virus with a seronegative partner
• Unexplained infertility
ASSOCIATED CONDITIONS
Causes of infertility

DIAGNOSIS
SIGNS AND SYMPTOMS
Inability to conceive
History
• Coital frequency
• Use of contraception
• Prior pregnancies from either partner
• Prior pelvic infections
• Gynecologic history
• Medication history
TESTS
Lab
• Semen analysis
• Sperm antibody testing
• Special tests
- Zona-free hamster sperm-penetration assay
- Bovine cervical mucus sperm-penetration test
• Drugs that may alter lab results
- Clomiphene citrate (Clomid) can cause poor cervical mucus secondary to its antiestrogenic effects at the level of the cervix.
• Disorders that may alter lab results
- Abnormal pH of vagina or cervical mucus
- Bacterial infection semen/mucus
Imaging
Hysterosalpingogram
Diagnostic Procedures/Surgery
Postcoital test (out of use, recent literature has discredited its effectiveness) (1,2)
Pathological Findings
• Chronic cervicitis
• Chronic prostatitis
DIFFERENTIAL DIAGNOSIS
• Primary female factor?
• Primary male factor?
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Intrauterine insemination should be closely timed with ovulation. Ovulation prediction kits detect the luteinizing hormone (LH) surge that precedes ovulation by 12-36 hours. Intrauterine insemination is performed the day of and/or the day after the LH surge.
• The volume of inseminate that can be transferred into the uterus is 0.25-0.5 mL. Small amounts are used to avoid cramping and flushing the oocyte out of the tube. The volume is also limited by space within the uterus.
• Intrauterine insemination is an office procedure. 1st, the position of the uterus is determined. A speculum is placed in the vagina and the cervix is visualized. The sample of washed sperm is placed into the uppermost portion of the uterine cavity using an insemination catheter with a disposable tuberculin syringe. Avoid touching the uterine fundus with the catheter tip. Occasionally a tenaculum is needed on the anterior lip of the cervix, to straighten the endocervical canal. Cervical dilatation or paracervical block is rarely required. The sample is injected slowly over 30-60 seconds.
SPECIAL THERAPY
Complementary and Alternative Medicine
Recent studies have supported the use of acupuncture as adjuvant therapy to IVF (3,4).
MEDICATION (DRUGS)
First Line
• Clomiphene (Clomid), FSH r human menopausal gonadotropins
- Menotropins may be used for controlled ovarian hyperstimulation, and ovulation may be initiated by the administration of human chorionic gonadotropin (HCG), a LH-like molecule.
• A recombinant LH product, choriogonadotropin- (Ovidrel), may be used subcutaneously for final follicular maturation and ovulation.
- Intrauterine insemination is performed 24-36 hours after HCG administration.
• Clomiphene predisposes to poor cervical mucus, which can adversely alter sperm/mucus interaction. Clomiphene may induce luteal-phase defects.
• Dosages
- Clomiphene: 50 mg/d for 5-7 days to induce ovulation
- FSH (Bravelle, Follistim, Gonal-F); 150 IU/d IM for 5 days to induce ovulation
- Menotropins (Pergonal, Repronex, Gonal-F, Follistim), utilized for superovulation induction: Dosage and length of administration depends on patient response
• Contraindications
- Uncontrolled thyroid and adrenal dysfunction
- Intracranial lesion
- High follicle-stimulating hormone (FSH) level, indicating primary ovarian failure
- Abnormal bleeding of undetermined etiology
- Ovarian cysts of unknown origin
- Hypersensitivity
- Pregnancy
• Precautions
- Multiple births: Clomiphene 8%, menotropins 25%
- Severe ovarian hyperstimulation (ascites, pleural effusion, dehydration, electrolyte imbalance, pain)
- Ovarian torsion
Second Line
Estrogen in follicular phase of cycle to improve mucus (conjugated equine estrogen 1.25-2.5 mg/d cycle days 5-12 or Estraderm patches 0.1-0.2 mg/d cycle days 5-12)
FOLLOW-UP
PROGNOSIS
• Virtually all resulting pregnancies occur within the 1st 6 treatment cycles. A 6-month treatment interval usually represents an adequate therapeutic trial.
• There is a significant but small effect of IUI therapy alone in treating unexplained infertility (5A). IUI has been shown to be effective when cervical factor is present (5, 6)[A].
• There is a documented increase in efficacy with combination of intrauterine insemination and controlled ovarian hyperstimulation (5, 6)[B].
• The highest success rates are seen with idiopathic or cervical factor problems.
• The poorest outcome is with male factor.
• Monthly fecundities of 14% have occurred with therapeutic inseminations utilizing fresh semen.
COMPLICATIONS
• Uterine cramping
• Mild vasomotor symptoms
• Infection
• Theoretical but unproven risk is development of antisperm antibodies in response to increase exposure of the immune system to sperm antigens
PATIENT MONITORING
• Patients on Clomiphene require an ultrasound or a bimanual exam on a monthly basis.
• Patients on menotropins require at least serum estradiol measurements and pelvic sonography to monitor ovarian response.
REFERENCES
1. Oei SG, Helmerhorst FM, Bloemenkamp KWM, et al. Effectiveness of the postcoital test: a randomized controlled trial. Br Med J. 1998;317:502.
2. Helmerhorst FM, Van Vliet HA, Gornas T, et al. Intra-uterine insemination versus timed intercourse for cervical hostility in subfertile couples. 2005 Oct 19;(4): CD002809.
3. Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: A randomized, prospective, controlled clinical study. Fertility Sterility. 2006.
4. Westergaard LG, Mao Q, et al. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: A prospective, randomized trial. Fertility Sterility. 2006.
5. Practice Committee of the American Society for Reproductive Medicine. Effectiveness and treatment for unexplained infertility. Fertility Sterility. 2004;82(Suppl 1):S160-163.
6. Cohlen BJ. Should we continue performing intrauterine inseminations in the year 2004? Gynecol Obstet Invest. 2005;59(1):3-13. Epub 2004 Aug 27. Review.
ADDITIONAL READING
Johnson K, Posner SF, Biermann J, et al. Recommendations to improve preconception health and health careUnited States. A report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. MMWR Rec. 2006;55(RR-6):1-23.
MISCELLANEOUS
For donor insemination, only frozen semen is used and only after a 6-month period of "quarantine" to minimize danger of transmission of HIV and other sexually transmitted diseases.