Yasmin: the reason why.

Oral contraceptives have been available for a little over 40 years and, during that time, many different formulations have been introduced. There have been dramatic dosage reductions of both the estrogen and progestogen components and various progestogens have been introduced over time. The properties of most progestogens used in oral contraceptives are very similar, differing mainly in potency. Oral contraceptives with progestogens having new and unique properties are needed. World-wide, around 20-30% of women of childbearing age use oral contraceptives and their use declines after the age of 35 years, with an accompanying increase in the rates of unintended pregnancy and elective termination. Incorrect use likewise gives rise to high unintended pregnancy rates. Use in Europe is higher than in other regions. Discontinuation because of unwanted effects and misperceptions is very common. Common misperceptions that prevent women from initiating oral contraceptive use are weight gain, cancer risks and that bleeding indicates a significant problem. Unwanted effects that commonly give rise to discontinuation are bleeding, nausea, weight gain, mood changes, breast tenderness and headaches. Discontinuation rates are high, particularly in the first year, and adolescents have the highest rates of discontinuation. Correct consistent use must be encouraged by taking pills at a regular time each day and by reinforcing that bleeding and other unwanted effects are not medically serious. Reinforcement of the non-contraceptive health benefits is very important and it needs to be emphasized that long-term use enhances these non-contraceptive benefits. Most non-contraceptive benefits are due to the progestogen component and its inhibition of ovulation. The new drospirenone-containing oral contraceptive (Yasmin, Schering AG, Berlin, Germany) offers the traditional non-contraceptive benefits; however, due to its unique antimineralocorticoid and antiandrogenic properties, new and unique benefits have been observed. Acne is well controlled, as would be expected from its inhibition of ovulation, antiandrogenic activity and lack of attenuation of the estrogen-mediated increase in sex hormone binding globulin. Its antimineralocorticoid activity gives rise to a reduction in fluid-related symptoms. The oral contraceptive containing 3 mg drospirenone with 30 microg ethinylestradiol DRSP/EE) has excellent efficacy since drospirenone is a potent progestogen, the corrected Pearl index being 0.09. This index is lower than those of many other oral contraceptives. Cycle control is excellent and comparable to that experienced with other oral contraceptives. A significant and consistent weight loss was seen with DRSP/EE compared to a reference preparation containing desogestrel. Day-to-day compliance and the duration of intake of an oral contraceptive are dependent on the woman's satisfaction with the pill she is taking. DRSP/EE meets these expectations and, with its new and unique non-contraceptive benefits, offers a real new choice to women.

Analysis of in vitro migration patterns of human spermatozoa by a petri dish-based horizontal column.

Spermatozoa are required to travel a considerable distance in vivo to meet the oocyte at the fertilization site. However, none of the existing in vitro tests critically evaluates migration of sperm to assess their potential of reaching the oocyte. On the other hand, an in vivo model is not suitable for this type of study because of ethical and technical constraints. In the present study we utilized a horizontal column technique to analyze sperm migration. Migratory characteristics of fresh, unwashed semen sperm and sperm undergoing various treatments were examined in vitro using a Petri dish-based horizontal fluid column. The procedure involved loading a sperm sample into the column and determining sperm concentration, motility, and viability at different column segments for different migration durations (6, 12, 24, 48, and 72 h). All sperm samples produced an exponential migration pattern in all durations of migration. Propagation along the column edge, tendency to exit from the column, and hiding in the blind pouches were some of the important characteristic features exhibited by the migratory sperm. Variations in migration patterns were documented among semen donors, between fresh and frozen semen, and between washed and unwashed sperm. Prolonged postejaculation time diminished migratory potential. The recovery of sperm in the column end was independent of seminal variables with the exception of oligozoospermia. These observations suggest that the Petri dish-based horizontal column is effective for analyzing sperm migration characteristics for prolonged periods. The potential of this migration assay in predicting the in vivo potential of spermatozoa to reach the fertilization site will be worth exploring.

Cycle control with oral contraceptives: A review of the literature.

Comparing the degree of cycle control provided by various oral contraceptives is problematic. The inherent limitations, small demonstrated differences, and differing methods of data presentation characteristic of these trials support the conclusion that it is almost impossible to compare the bleeding patterns of one preparation with those of another. Chlamydial infection, smoking, and inconsistency of use are factors that have significant effects on rates of spotting and breakthrough bleeding. Clinicians must alert patients to the possibility of intermenstrual bleeding and educate them with regard to the importance of continued, consistent oral contraceptive use to minimize those problems among pill users in their practices.

Update on androgenicity.

The development of a new generation of progestins deemed less androgenic than their earlier counterparts has led to a number of misconceptions regarding their possible benefits in combination oral contraceptives. All combination oral contraceptives are beneficial for treating such androgenic conditions as acne and hirsutism. The only expressed androgenic effect of some first- and second-generation combined oral contraceptives are changes in plasma lipid and lipoprotein levels. However, the overall effect of today's low-dose oral contraceptives is largely lipid neutral, and human and monkey studies have shown that oral contraceptive use is associated with reduced, not increased, atherosclerosis rates. Myocardial infarction rates are not increased among oral contraceptive users, except among those who are heavy smokers.

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.

PIP: Oral contraceptives (OCs) 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 2 OCs containing the same amounts of ethinyl estradiol (EE, 20 mcg) but different progestins, levonorgestrel (LNG, 100 mcg), and norethindrone acetate (NETA, 1000 mcg). 58 healthy women aged 18-28 years received 3 cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in 3 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 mcg) 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 T.

Protecting the endometrium. Opposing the hyperplasia/malignancy potential of ERT.

Many trials have examined the clinical and histologic effects of various hormone replacement therapy combinations with the objective of minimizing the incidence of hyperplasia and the potential for subsequent development of adenocarcinoma. Reviewing the results of these trials, it appears that high-dose, long-term progestogen therapy is effective in protecting the endometrium, with duration having a greater impact than dose. Among women given 0.625 mg conjugated equine estrogen (CEE), sequential regimens should include 5 or 10 mg medroxyprogesterone acetate (MPA) or 200 mg micronized progesterone for 12 days or more. Continuous combined regimens require 2.5-5 mg MPA. With women who are taking 1.25 mg CEE the data are less clear, but recommendations include administration with 10 mg MPA for 12-14 days or 5 mg MPA continuous combined therapy.

Vaginal bleeding patterns in women receiving hormone replacement therapy. Impact of various progestogen regimens.

Postmenopausal bleeding is more prevalent than was previously thought, occurring in women regardless of whether or not they are on hormone replacement therapy. While estrogen-only regimens have been used for several beneficial effects, bleeding patterns associated with these regimens can be irregular and unpredictable, causing discomfort to the patient as well as increasing the risk of both endometrial hyperplasia and carcinoma. Studies in recent years have examined the effects of estrogen-only regimens as compared to different estrogen-plus-progestogen combination therapies to help regulate and minimize postmenopausal bleeding while providing endometrial protection.

Time course of hypo-osmotic swellings of human spermatozoa: evidence of ordered transition between swelling subtypes.

The hypo-osmotic swelling test (HOST or HOS test) usually takes into consideration the total HOS response value with no emphasis either on the value of the response subtypes or the response evaluation time. This study investigated the time course of HOS responses and analysed their physiological relevance. Raw semen spermatozoa and Percoll washed spermatozoa were used in the experiment. The morphological changes in the sperm tail were monitored by incubating the spermatozoa in the hypo-osmotic solution for 16 different time periods. The HOS reactive spermatozoa and the type of HOS reaction (swelling subtypes) of the samples subjected to different duration of treatment were identified under a phase contrast microscope. Also the fate of individual spermatozoa in a hypo-osmotic environment were monitored for 30 min. In spermatozoa exposed to a hypo-osmotic solution, the motility lasted usually less than 2 min and motility characteristics were uniquely different from that of the spermatozoa under iso-osmotic conditions. The HOS response development was permanent but the motility loss due to hypo-osmotic shock was reversible up to 1 min of incubation. There was an indication of ordered transition among the HOS swelling subtypes apparently initiating with subtype b destined to c, d, e, f and g. Further, the subtypes a and g showed gradual decrease and increase, respectively, while subtype b showed abrupt initial increase and then gradual decrease. Transition from b to g could be direct or via one or more than one subtypes. Ultrastructure based analysis indicated that HOS response subtypes are the apparent reflection of the differences in the cytoskeletal assembly of the sperm tail and thus may be identifying different physiological variants in the sperm population. These results indicate that shorter incubation is essential to document the kinetics of various HOS responses but the conventional HOS test misses these important HOS features because of lengthy incubation. Since the time course of ordered transition of HOS responses will vary more than the total HOS response in semen of different aetiologies, the importance of HOS response subtypes and response evaluation time should be taken into consideration when applying HOS test.

Preconceptional sex selection: past, present, and future.

Predetermination of sex in human and in farm animals is reviewed. Preconceptional sex selection has generated great interest and controversy over the years. Medical and commercial benefits outweigh the ethical issues. Technology has not yet provided a routine method for separating the X- and Y-chromosome-bearing sperm. Flow cytometry is the only technique that produces a clinically significant enrichment of X- or Y-bearing spermatozoa However, concern has been raised about the methodological implications of the flow technique because of the use of DNA stains and UV light. Some other techniques, such as gradient columns, appear to produce a slight enrichment of one type of sperm over the other, but this level of enrichment appears unlikely to affect the sex ratio at birth. It thus remains speculative whether 100% pure preparation of X or Y sperm can be obtained unless a major improvement in methodology is achieved. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are currently the methods of choice for evaluating the validity of the sex selection procedure. In view of the extraordinary pace of the technological and scientific progress, it can be expected that the clinical and commercial application of the technology of preconceptional sex selection by X and Y sperm separation will be a reality in near future.

Assessment of the relationship of sperm morphology with seminal and other clinical conditions of semen donors.

The occurrence of abnormal forms of spermatozoa in human semen is quite common. According to WHO, semen is considered normal even if it contains 50% morphologically abnormal spermatozoa. This study assessed whether the sperm morphology maintains any relation with the relevant clinical conditions of the semen donor. One hundred samples representing normal and different types of male factor etiologies underwent semen and morphological analysis. Clinical information such as race, age, weight, profession, medication, medical history, and smoking habit of the semen contributors were recorded. The influence of seminal and clinical features on sperm morphology was evaluated with multiple regression analysis. Head abnormalities were more common than tail abnormalities. Acrosomal defects and coiled tails were the most prevalent head and tail abnormalities, respectively. Regression analysis failed to confirm any strong association between sperm morphology and other seminal parameters. Accessory gland-related seminal parameters such as viscosity, volume, pH, and liquefaction showed the least association with the morphological variability. Sperm morphology also showed poor correlation with race, age, weight, smoking habit, and work environment.

Assessment of the quality of frozen serum by spectrophotometric analysis and sperm bioassay.

Serum is an integral part of media used for in vitro fertilization (IVF) and andrology work. Previous studies showed that the IVF results could benefit if sera were screened for deleterious effects before use. Such screening is impractical when fresh sera are used but may be feasible if the serum is frozen prior to use. This study assessed the impact of freezing on the quality of serum. A total of 158 serum samples, prepared in a university-based andrology-IVF center, were included in the study. The frozen sera were thawed in batches to be used in a series of laboratory experiments. Serum quality was evaluated by spectrophotometric analysis and sperm bioassay under several defined conditions: fresh, frozen, pre- and postfiltration, pre- and postcentrifugation, and the patients' fertility condition. Although all sera were filtered through 0.22-micron filter, more than 10% frozen sera required 0.4- or a combination of 0.8- and 0.4-micron filters before they could be passed through the 0.22-micron filter. Frozen sera that were directly filtrable with a 0.22-micron filter lost 13% turbidity upon filtration. The turbidity of the frozen sera were higher compared to fresh ones as revealed by optical density (OD) and relative light scattering (RLS) spectrophotometry. The freeze/storage-induced spectrophotometric changes did not correlate with the storage time. The centrifugation caused precipitation of sera components. The rate of precipitation of the serum components correlated with the duration of freezing. Spectrophotometric analysis and sperm bioassay did not differentiate the sera of pregnancy-positive and pregnancy-negative subjects. The sperm bioassay failed to detect any biological impact of freezing-induced spectrophotometric changes in the sera, suggesting that the freezing-induced changes did not significantly diminish the serum's capability of supplementing the culture media.

Absence of flow in ovarian vein by time-of-flight magnetic resonance angiography without evidence of thrombosis.

A case of absent flow in the left ovarian vein was diagnosed on time-of-flight (TOF) magnetic resonance angiography (MRA) while investigating for pelvic vein thrombosis in a 53-year-old female. This appearance should not be misdiagnosed as a sign of ovarian vein occlusion or thrombosis. Magnetic resonance imaging (MRI) is a sensitive noninvasive imaging modality in such a clinical setting. Familiarity with the potential pitfalls of different MRA techniques is essential for correct diagnosis. A review of different MRA techniques in evaluation of pelvic venous thrombosis is presented.

Modified guanidinium thiocyanate method for human sperm DNA isolation.

Mammalian sperm chromatin is highly condensed, so isolating DNA from such chromatin can be a formidable task. The procedures that produce high quality DNA from somatic cells fail to yield quality sperm DNA. In this study we have modified the previously used guanidinium method to make it simple and efficient in isolating human sperm DNA. In our method, the lysis buffer contained guanidinium, sodium citrate, sarkosyl, proteinase K and mercaptoethanol. Proteinase K was not used in the original guanidinium method but was included in our protocol. CsCl centrifugation of the lysate, as described in the original procedure, was omitted. Instead, isopropyl alcohol was added directly to the lysis buffer to harvest the DNA. This modified guanidinium method generated high molecular weight DNA while the other two methods resulted in considerable DNA degradation. There was no difficulty in restriction enzyme digestion of DNA prepared by the modified method as revealed by Southern blot analysis. Since the modified guanidinium method is a simple one-step procedure which avoids homogenization, organic solvents, centrifugation and, more importantly, produces degradation-free DNA, it could be the method of choice when DNA from mature germ cells is needed.

Human sperm bioassay has potential in evaluating the quality of cumulus-oocyte complexes.

Human sperm bioassay is routinely used as a quality control check for the culture media. This is one of the three bioassays chosen by the College of American Pathologists (CAP) for interlaboratory proficiency testing to assess the standards of in vitro fertilization (IVF) and andrology laboratories. This study utilized sperm bioassay to assess the quality of cumulus-oocyte complexes (COCs) retrieved in IVF procedures COCs, harvested from the female partner of IVF couples, undergoing identical ovarian stimulation protocols, were individually inseminated with the sperm of the corresponding male partner. Sperm motility in sperm-COC cocultures were compared. Cocultures were established by inseminating the 103 COCs, retrieved from 18 IVF couples with 1 x 10(5) to 2 x 10(5) sperm of the corresponding male partners of the couples. In all 18 cases, the sperm were prepared identically using the Percoll wash method. The cocultures were maintained for 48 h but the oocytes were removed immediately after the fertilization check (approximately 16 h). The motility of sperm in the cocultures and in the insemination stocks were noted and 17 of 18 sperm stocks used for insemination had similar high preinsemination motility (90.2 +/- 5.0%). At 48 h the sperm motility had significantly decreased in the cocultures compared to the insemination stocks; 52.7 +/- 19.9% versus 67.2 +/- 10.4%. There was no difference in the motility among the small, medium, and large COCs (56.4 +/- 24.6%, 52.5 +/- 17.9%, and 50.8 +/- 20.9%, respectively). In 45% of IVF cases, the motility in cocultures varied widely, falling below as well as above that of their corresponding insemination stocks. Furthermore, the sperm motility varied among the cocultures in both pregnant and nonpregnant patients but the extent of variation appears to be greater in the latter. The inter-COC coculture sperm motility variation most likely is due to the differences in the quality of cumulus-oocyte complexes.

Practical aspects of hormone replacement therapy.

Menopause is an endocrinopathy characterized by hypoestrogenism. Estrogen can be replaced easily. Available preparations can be taken by mouth, intramuscularly, transdermally, or transvaginally. Unopposed estrogens increase the risk of endometrial cancer, which can be overcome by the concomitant administration of a progestin agent. The progestin can be administered cyclically either every month, resulting in a monthly menses, or every 3 months, resulting in menses every 3 months. The progestin can also be administered every day, which achieves amenorrhea in over half of the patients; the remainder have breakthrough bleeding. Abnormal bleeding can be assessed by either endometrial biopsy or transvaginal ultrasound.

Contraception in women older than 40 years of age.

Women older than 40 years have high rates of unwanted pregnancy and abortion and traditionally have had limited choices of contraception agents. In today's market, oral contraceptives should be considered as should IUDs in properly screened candidates. Sterilization is effective for the couple who knows that they will have no more children. Mechanical methods are effective if used when intercourse tends to be a planned event and infrequent. With the variety of agents available in today's market, there is no reason why the unwanted pregnancy rate and abortion rate of the women older than 40 should not be reduced dramatically.

PIP: Women over age 40 have high rates of unwanted pregnancy and abortion and limited choices of contraception. Oral contraceptives (OCs) with 20-35 mcg of estrogen can be recommended for these women as long as they do not smoke. Previously, some association was found between pill users aged over 35 years and an increased risk of myocardial infarction. Thus, OCs were not recommended for them. However, recent findings implicate smoking instead of age in the increased risk of myocardial infarction in OC users. OCs are useful in treating dysfunctional uterine bleeding of the perimenopause, in regulating menstrual cycles, and in preventing anemia. Other benefits include the reduction of endometrial and ovarian cancers, fibroids, endometriosis, benign breast diseases, ovarian cysts, ectopic pregnancy, and pelvic inflammatory disease. Monogamous and parous women with negative cervical cultures for gonorrhea and chlamydia can use IUDs. Sterilization is an option only after the completion of family size; tubal ligation, however, is associated with more morbidity and mortality than vasectomy. Thus, vasectomy should take precedence over tubal ligation. Depo-Provera injections every 3 months are safe, and they also help with dysfunctional bleeding and breakthrough bleeding via the production of amenorrhea. This drug is approved by the Food and Drug Administration and is popular worldwide. Long-term studies have not confirmed the increased risk of breast cancer with Depo-Provera use. Among implants, Norplant is almost as effective as tubal ligation, but it may cause dysfunctional bleeding in women over the age of 40. Mechanical methods also provide protection; however, they result in a pregnancy rate of 10-20% per year.

Medical management of abnormal uterine bleeding in the patient in her 40s.

A large proportion of AUB can be controlled successfully with a variety of pharmacologic agents.