REPRODUCTIVE HEALTH ISSUES
| UPDATE ON NEW FORMS OF CONTRACEPTION —Julia V. Johnson, MD, Professor and Vice Chair for Gynecology, and Director of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington |
| Advantages of current contraceptive choices: predictable efficacy, minimal side effects, ease of reversibility, and limited short-term and long-term risks; risks remain low for all forms of contraceptives; risk for venous thromboembolism—markedly reduced with low-dose contraceptives, compared to risks of pregnancy; 0.4 to 1.0 per 10,000 women in general population; continuing research may show risk decreased even further; myocardial infarction and stroke—recent data show no increased risk in women of any age; limited data show smokers who use low-dose contraceptives may not be at increased risk; breast cancer—World Health Organization analysis of >100,000 women on oral contraceptives found no increased risk; increased risk seen only in younger women (likely surveillance bias); duration of use, family history, parity, and age not factors for increased risk in women using hormonal contraceptives; women rarely aware that risk for reproductive cancers decreases with use of hormonal contraceptives |
| Advantages of new contraceptives: efficient and efficacious; minimal side effects; limited short- and long- term risks; pharmaceutical companies primarily concerned with patient satisfaction; nonoral hormonal contraceptives increasingly popular because of ease of use and longer duration of effectiveness; noncontraceptive benefits— treatment for medical disorders, ie, menorrhagia, dysmenorrhea, and premenstrual syndrome; hematologic benefits; acne and hirsutism |
| Levonorgestrel intrauterine system (IUS): inhibits fertilization by thickening cervical mucus and affecting sperm motility; suppresses endometrium; levonorgestrel released over time; only fraction of level obtained with oral levonorgestrel; progestin component has primarily local effect on endometrium and less systemic effect; used as treatment for menorrhagia in Europe; ≈70% reduction in menorrhagia; ≈80% reduction in dysmenorrhea; recent studies show improvement in endometriosis and symptomatic fibroids |
| Contraceptive implants: excellent effectiveness; minimal side effects; bleeding relatively modest; levonor-gestrel implant (Norplant)—6 capsules; 5 to 7 yr of effectiveness; excellent efficacy; concern with discomfort and appearance of capsules and removal of capsules; Norplant II (called Jadelle in Europe) uses 2 capsules; effective for 5 yr; efficacious; etonogestrel (Implanon)—single rod; effective for 3 yr; progestin; highly efficacious and easy to insert and remove; future options—medroxyprogesterone acetate in 4 to 5 capsules; other single-rod progestins being investigated |
| Injectable contraceptives: medroxyprogesterone acetate (Depo-Provera)—highly efficacious; requires quarterly injection; new subcutaneous injection for self-administration; medroxyprogesterone acetate plus estra--diol (Lunelle)—no longer on market; monthly injection; allowed for monthly menstrual cycles; comparison of injectables and other contraceptive methods—highly efficacious; do not have problem of user- dependent efficacy associated with oral contraceptives; 1-mo effectiveness with medroxyprogesterone acetate and estradiol cypionate (MPA/E2 C) and 3-mo effectiveness with continuous progestin (depo-medroxyprogesterone acetate); more rapid return to fertility and fewer problems with abnormal bleeding with MPA/E2 C |
| Hysteroscopic tubal sterilization: permanently inserted expandable spring device (stainless steel inner coil and titanium alloy outer core); optimal placement 5 to 10 mm out of ostium; trial data show placement problem in ≈2% of patients; other complications <1%; 100% tubal occlusion in initial phase 2 trials; average time for placement ≈10 min; total operating/recovery room time ≈1.5 hr; can be performed using small hysteroscope; no difference in reported discomfort with intravenous sedation or local anesthesia; 95% success in placement (leaving out failure-to-place cases); 96% tubal occlusion 3 mo after procedure, remaining 4% had tubal occlusion 6 mo later |
| Future contraceptive options: additional hysteroscopic tubal sterilization methods; new implant systems in phase 1 or 2 trials; preliminary data from China show progestin and testosterone reasonable male hormonal contraceptive; new nonsteroidal progestin; good evidence RU486 prevents ovulation; delivery system for antiprogestin contraceptive most likely intrauterine device |
| ADVANCES IN THE DIAGNOSIS AND TREATMENT OF INFERTILITY— Peter Casson, MD, Associate Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Vermont College of Medicine; Director, Vermont Center for Reproductive Medicine, Burlington |
| General considerations: infertility defined as inability to achieve pregnancy after 1 yr of unprotected intercourse; time modified to 6 mo in women >35 yr of age; infertility considered disease; traumatic, emotional, spiritual, and societal implications; delayed childbearing associated with slight increase in prevalence; prevalence remains 10% to 15%; because of more treatment options, couples no longer suffer in silence; effect of advanced reproductive age—fertility rate declines significantly after 35 yr of age because of diminished ovarian reserve; ovulated eggs of decreased quality, and miscarriage rate increased; 50% chance of miscarriage at 44 yr of age, and likelihood of achieving viable pregnancy significantly decreased |
| Types of infertility: infertility often has >1 cause; male factor 23% to 30%; ovulatory dysfunction ≈20%; tubal damage less frequent cause; endometriosis and coital problems uncommon but reasonable causes; cervical factor; unexplained causes account for about one third of cases; segregates into 2 subgroups; often unexplained infertility simply represents diminished ovarian reserve or male factor infertility |
| Work-up: establish ovulation—95% to 98% chance woman ovulatory if she has regular menses (28-32 days) with periovulatory and moliminal symptoms, ie, breast tenderness, bloating, periovulatory spotting, or pain; basal body temperature (BBT) charting—pro--gesterone has central hypothalamic stimulatory action; rise in progesterone represents change of 0.8°F; ovulation occurs during shift in BBT; ovulation easy to determine retrospectively, more difficult prospectively |
 | Tests for determining ovarian reserve: cycle day 3 follicle-stimulating hormone (FSH)—probably best test; concern if FSH >10 mIU/mL; other tests— cycle day 3 estradiol, clomiphene challenge test, antral follicle count (> 20 follicles indicative of normal ovarian reserve) and hysterosalpingography (HSG) |
| Tests for determining male factor infertility: semen analysis—sperm motility time dependent; look for >1 mL volume; count should show >20 million/mL with 50% motility; different ways to measure morphology, eg, Kruger’s strict criteria (8% or 9% normal forms); urologic evaluation—urologic conditions can cosegregate with testicular problems, eg, varicocele, cancer |
| Ovulation induction: polycystic ovarian syndrome most common reason for anovulation, ≈50% hyperinsulinemic variant; rule out hypothalamic causes, eg, exercise, stress, thyroid disease, prolactin; speaker prescribes metformin XR at dinner (improves tolerability); metformin improves in vitro fertilization (IVF) outcomes; clomiphene (150 mg/day); if not successful, human menopausal gonadotropins used (hMG; can result in multiple gestations) |
| Current treatments for infertility: ovulation induction in anovulatory patient, empiric therapy in unexplained infertility, donor sperm, and IVF; donor sperm—effective; relatively inexpensive; relatively low rate of multiple gestations; national standards for sperm banks have increased safety; understated treatment for male factor infertility |
| IVF: multiple mature oocytes mixed with sperm in vitro; 2 or 3 embryos placed in uterus via ultrasonography (US)-guided technique; medications commonly used include oral contraceptives, leuprolide (Luprone), FSH, and leuteinizing hormone; eggs harvested by US-guided oocyte retrieval; 2 or 3 embryos transferred to uterus 3 days later, and woman put on progesterone; 35% success rate; Society of Assisted Reproductive Technology (SART) IVF outcomes 2001—21,000 live-birth deliveries in 80,000 cycles (31.4% success rate); IVF quantifiable area of medicine; benefits—intracytoplasmic sperm injection (ICSI) revolutionized treatment of male factor infertility; need for extensive diagnosis of infertility eliminated; rendered most fertility surgery obsolete; best way to control multiple gestations; treatment outcomes tracked and available to patients; no longer treatment of last resort and becoming first-line therapy; birth rate through IVF significantly improved (≈33%); free market has controlled expense for procedure and cost continues to fall; clinical pregnancy rate with IVF cumulative and linear; cumulative pregnancy rate after 3 cycles close to 90%; utilization of IVF increasing; 5% of children in Scandinavia born as result of IVF |
| Intracytoplasmic sperm injection: single sperm injected into cytoplasm of oocyte; pregnancy rate equivalent to normal IVF; does not appear to increase miscarriage rate; has not dramatically increased birth defect rate; has revolutionized management of male factor infertility; has facilitated sperm retrieval at vasectomy reversal, microsurgical epididymal sperm aspiration, and testicular sperm extraction |
| Work-up for infertility: extensive work-up no longer necessary because pregnancy rates same, except when infertility caused by diminished ovarian reserve; recommended tests include cycle day 3 FSH, thyroid-stimulating hormone, prolactin, rubella, progesterone, sperm count, and HSG; empiric therapy with unexplained infertility; be aware of time frame if patient >35 yr of age; consider IVF early in diagnosis; IVF rendered most fertility surgery obsolete; fertility surgery generally limited to removal of endometriomas, ensuring vaginal ovarian access, and normalizing uterine cavity in attempt to enhance IVF |
| Multiple gestations: major reason insurance companies do not cover IVF; higher pregnancy rate not achieved with increased number of embryos; transferring >2 embryos increases triplet rate (0.9%); recommended that 2 embryos be transferred if woman <36 yr of age and single embryo transfer if patient <30 yr of age; pregnancy rate with single embryo transfer decreases slightly (cost issue for patients) |
| Complications of IVF: cost (up to $15,000); ovarian hyperstimulation syndrome (uncommon); risks of retrieval (uncommon); birth defects—Australian database demonstrated doubling of birth defect rate in children as result of IVF; however, Belgiuan database showed no increase; SART database did not show increase in birth defects; speaker opines small increase likely and probably slight increase in sex chromosome disorders with ICSI; reports of imprinting disorders, ie, Beckwith-Wiedemann and Angelman Syndrome, rare |
| New developments in IVF: single-cell embryo biopsy and preimplantation genetic diagnosis (PGD) allow for diagnosis of genetic disease and identification of chromosomally abnormal embryos; designer babies most likely significant issue in future; sex selection becoming more mainstream |
| How to help infertility patients: obtain cycle day 3 FSH; ensure semen analysis handled by reputable laboratory; confirm that patient ovulatory; gently remind patient that time of essence in fertility; do not lose valuable time with empiric therapy, eg, clomiphene, BBT charting, and reproductive surgery |
Educational Objectives
| The goal of this program is to provide the listener with an update on contraception and provide them with a better understanding of the diagnosis and treatment of infertility. After hearing and assimilating this program, the clinician will be better able to: |
| Discuss the benefits of currently available contraceptive options. |
| Evaluate the risks associated with hormonal contraceptives. |
| Recommend an appropriate form of birth control. |
| Define infertility and discuss the diagnostic modalities for infertility. |
| Discuss in vitro fertilization as a treatment option for infertility. |
Discussed on This Program
Clomiphene citrate [Clomid, Milophene, Serophene] Etonogestrel [Implanon] Glipizide/metformin HCl [Metaglip] Leuprolide acetate [Eligard, Lupron, Lupron Depot, Lupron Depot – 3 month, Lupron Depot – 4 month, Lupron Injection, Lupron Depot-Ped, Lupron for Pediatric Use, Viadur] Levonorgestrel implant [Capronor {investigational}, Norplant System] Medroxyprogesterone acetate [Amen, Curretab, Cycrin, Depo–Provera, Hematrol, Provera] Medroxyprogesterone acetate/estradiol cypionate (MPA/E2 C) [Lunelle] Metformin HCl [Fortamel, Glucophage. Glucophage XR]
Suggested Reading
Erel CT et al: Is laparoscopy necessary before assisted reproductive technology? Curr Opin Obstet Gynecol 17(3):243, 2005; Hamberger L et al: Avoidance of multiple pregnancy by use of single embryo transfer. Minerva Ginecol 57(1):15, 2005; Lakha F et al: The acceptability of self-administration of subcutaneous Depo-Provera. Contraception 72(1):14, 2005; Magos A et al: Hysteroscopic tubal sterilization. Obstet Gynecol Clin North Am 31(3):705, 2004; Rager KM: No bones about it-depot medroxyprogesterone acetate remains an excellent contraceptive option for adolescents. J Pediatr Adolesc Gynecol 18(3):187, 2005; Schieve LA et al: Spontaneous abortion among pregnancies conceived using assisted reproductive technology in the United States. Obstet Gynecol 101(5 Pt 1):959, 2003; Schieve LA et al: Live-birth rates and multiple-birth risk using in vitro fertilization. JAMA 282(19):1832, 1999; Shulman LP: Advances in female hormonal contraception: current alternatives to oral regimens. Treat Endocrinol 2(4):247, 2003; Wiggins DA et al: Outcomes of pregnancies achieved by donor egg in vitro fertilization-A comparison with standard in vitro fertilization pregnancies. Am J Obstet Gynecol 192(6):2002, 2005; Wright VC et al: Assisted reproductive technology surveillance—United States, 2002. MMWR Surveill Summ 54(2):1, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed: Dr. Johnson is on the Speaker’s Bureau for Wyeth and Novo Nordisk and has been involved in research with Wyeth, Pharmacia, Proctor & Gamble, and Novo Nordisk.
Dr. Johnson was recorded at the 26th Annual Postgraduate Course in Obstetrics & Gynecology, sponsored by the University of Vermont College of Medicine, held on September 27-29, 2004, in Burlington, Vermont. Dr. Casson was recorded at Women’s Health Issues: Perception, Prevention & Practice, sponsored by the University of Vermont College of Medicine, held on May 12-14, 2005, in Burlington, Vermont. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
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