Karen D. Bradshaw

A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm

Cryopreserved sperm have lowered fertility when compared with fresh sperm in artificial insemination by donor programs. The purpose of this study was to compare pregnancy rates following intrauterine insemination (IUI) and intracervical insemination (ICI) with cryopreserved sperm in a prospective trial using the patient as her own control. A total of 154 patients were randomized into alternating treatment cycles and underwent 238 cycles of IUI and 229 cycles of ICI. The pregnancy rate per treatment cycle was 9.7% following IUI and 3.9% following ICI. Treatment outcome was influenced by patient age, ovulatory status, and endometriosis. Pregnancy success correlated well with the post-thaw survival of sperm and the number of motile cells inseminated. In spite of having normal semen parameters, some donors were found to have markedly reduced sperm fecundity. We conclude that IUI with cryopreserved sperm can be an effective treatment for couples with infertility, genetic indications, or other reasons.

Effect of low-dose oral contraceptives on androgenic markers and acne

Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.

Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: A prospective, randomized, crossover study during intrauterine insemination cycles

OBJECTIVE To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles. PATIENTS Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study. SETTING Tertiary academic medical center. DESIGN Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles. RESULTS Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle). CONCLUSIONS If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.

Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: An up-to-date review

ObjectiveMenopause and its transition represent significant risk factors for the development of vulvovaginal atrophy-related sexual dysfunction. The objective of this study was to review the hormonal and nonhormonal therapies available for postmenopausal women with vulvovaginal atrophy-related sexual dysfunction, focusing on practical recommendations through a literature review of the most relevant publications in this field. MethodsThis study is a literature review. ResultsAvailable vaginal estrogen preparations are conjugated equine estrogens, estradiol vaginal cream, a sustained-release intravaginal estradiol ring, or a low-dose estradiol tablet. Vaginal estrogen preparations with the lowest systemic absorption rate may be preferred in women with history of breast cancer and severe vaginal atrophy. Vaginal lubricants and moisturizers applied on a regular basis have an efficacy comparable with that of local estrogen therapy and should be offered to women wishing to avoid the use of vaginal estrogens. ConclusionsOral, transdermal, or vaginal estrogen preparations are the most effective treatment options for vulvovaginal atrophy-related sexual dysfunction. Selective estrogen receptor modulators such as lasofoxifene and ospemifene showed a positive impact on vaginal tissue in postmenopausal women. Vaginal dehydroepiandrostenedione, vaginal testosterone, and tissue selective estrogen complexes are also emerging as promising new therapies; however, further studies are warranted to confirm their efficacy and safety.

Abnormal uterine bleeding in adolescents

Irregular bleeding is a common complaint of adolescents and is responsible for approximately 50% of gynecologic visits in that age group. Most abnormal bleeding in adolescents is caused by immaturity of the hypothalamic-pituitary-ovarian axis resulting in anovulation. Approximately 20% of adolescents have an underlying disorder requiring targeted diagnostic testing. A thorough history and physical examination and laboratory findings will often reveal the source of abnormal bleeding. Appropriate treatment is then directed to the underlying cause.

Comparison of bicarbonate and HEPES-buffered media on pregnancy rates after intrauterine insemination with cryopreserved donor sperm *

OBJECTIVE We compared the pregnancy rates (PRs) after intrauterine insemination (IUI) with frozen donor sperm prepared in Hams F-10 medium (Irvine Scientific, Santa Ana, CA) with bicarbonate buffer and synthetic human tubal fluid with HEPES buffer (Irvine Scientific). DESIGN Women (n = 101) were randomized upon entry into the program, receiving sperm prepared in either Hams F-10 or human tubal fluid medium their first treatment cycle. If pregnancy did not occur, the alternate medium was used to prepared sperm for the following cycle. SETTING All patients were treated in our private care center. PATIENTS Patients entering this study were normally ovulating women undergoing IUI with frozen donor sperm. MAIN OUTCOME MEASURE Pregnancy was used as our main outcome measure of success. RESULTS After 324 cycles of treatment, the PR per cycle of IUI was 17.5% with sperm prepared in human tubal fluid which was significantly different (P = 0.05) from the PR (9.8%) after insemination with sperm prepared in Hams F-10. There was no statistical difference in the number of motile cells inseminated in each of these groups. CONCLUSIONS Transitory exposure of the sperm in Hams F-10 medium to the environment during preparation for insemination may result in an alkalinization of the medium that has a lasting influence on sperm fertility.

Cumulative pregnancy rates for donor insemination according to ovulatory function and tubal status

From our study of 234 cases of AID with fresh semen, we conclude the following: (1) women who do not have other infertility problems, such as ovulatory dysfunction or evidence of tubal disease, have approximately a 90% chance of pregnancy if they stay in the program for up to 12 cycles; (2) with even greater persistence (i.e., greater than 12 cycles), it is predicted that virtually 100% of these women would conceive, but this conclusion is based on extrapolated data and therefore must be interpreted with caution; (3) women with ovulatory dysfunction who are treated with CC during their AID cycles ultimately achieve the same likelihood of pregnancy as women with normal ovulatory function, but at a slower rate; and (4) women with one patent tube (possibly a marker for generalized tubal damage) have a poorer outcome from AID than those with bilaterally patent tubes, from the standpoint of both the ultimate likelihood of pregnancy and the pregnancy rate per cycle.

Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: a prospective, randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVE The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism. DESIGN Prospective, randomized, double-blind, placebo-controlled, crossover trial. SETTING Clinical research center, university hospital. PATIENT(S) Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy. INTERVENTION(S) Collection of serum and urine samples and measurement of bone density. Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks. RESULT(S) In both protocol A and B, LH and E(2) levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). CONCLUSION (S): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.

Autologous buccal mucosa graft augmentation for foreshortened vagina.

BACKGROUND: Vaginal foreshortening after pelvic surgery or radiotherapy may lead to dyspareunia and decreased quality of life. Unfortunately, little literature exists regarding treatment options for this debilitating problem. Autologous buccal mucosal grafting has been previously reported for creation of a total neovagina and the repair of postvaginoplasty vaginal stenosis. TECHNIQUE: Autologous buccal mucosa offers several advantages as a replacement material for vaginal reconstruction. Vaginal and oral buccal mucosa are both hairless, moist, nonkeratinized stratified squamous epithelia. Buccal mucosa has a dense layer of elastic fibers, imparting both elasticity and strength, and acquires a robust neovascularity with excellent graft take. The graft material is readily available and donor site scars are hidden in the mouth. EXPERIENCE: A 60-year-old woman had vaginal foreshortening to 4.5 cm 15 years after radical hysterectomy and brachytherapy for endometrial cancer. She was unable to have intercourse despite attempted vaginal dilation. Her foreshortened vagina was successfully augmented with autologous buccal mucosa grafting at the apex, increasing her vaginal length to 8 cm and permitting pain-free intercourse. CONCLUSION: Even in the face of an altered surgical field after radical hysterectomy and radiation, autologous buccal mucosa is an option for vaginal reconstruction for vaginal foreshortening.

Disorders of Pubertal Development

Puberty is a complex developmental process that culminates in sexual-maturity. This transitional period begins in late childhood and is characterized by maturation of the hypothalamic—pituitarygonadal axis, the appearance of secondary sexual characteristics, acceleration of growth, and ultimately the capacity for fertility. Significant endocrinologic changes accompany these developmental events. This chapter reviews the physiologic changes of normal puberty and examines the causes of precocious and delayed sexual maturation.