As the world grows: contraception in the 21st century.

Contraceptives that are readily available and acceptable are required in many poorer countries to reduce population growth and in all countries to prevent maternal morbidity and mortality arising from unintended pregnancies. Most available methods use hormonal steroids or are variations of barrier methods. Reports from several fora over the last 12 years have emphasized the number of unwanted pregnancies and resultant abortions, which indicate an unmet need for safe, acceptable, and inexpensive contraceptive methods. This unmet need can be assuaged, in part, by development of new nonhormonal contraceptive methods. This Review addresses the contribution that the "omic" revolution can make to the identification of novel contraceptive targets, as well as the progress that has been made for different target molecules under development.

Oral administration of the cyclooxygenase-2 (COX-2) inhibitor meloxicam blocks ovulation in non-human primates when administered to simulate emergency contraception.

BACKGROUND: Prostaglandins produced via cyclooxygenase-2 (COX-2) within the periovulatory follicle are required for successful ovulation. Inhibition of follicular prostaglandin synthesis prevents timely follicle rupture and oocyte release. This study was conducted to determine if a 5-day course of oral administration of the COX-2 inhibitor meloxicam can prevent ovulation while maintaining normal menstrual cycles in non-human primates. METHODS: Adult female cynomolgus monkeys were studied in each of four sequential menstrual cycles. In Cycle 1, a serum sample was obtained each day and assayed for estradiol, progesterone and luteinizing hormone; first menses was also noted to establish parameters of a normal menstrual cycle for each animal. In Cycle 2, meloxicam was administered orally once each day for 5 days beginning at either mid follicular (n = 4), late follicular (n = 4) or periovulatory (n = 4) phase of the menstrual cycle; daily serum samples and menses were assessed as for Cycle 1. In Cycle 3, the follicle-bearing ovary was removed 2 days after the expected day of ovulation (n = 3-4/treatment group). In Cycle 4, monkeys received the 5-day courses of oral meloxicam as in Cycle 2 (n = 3-4/treatment group), and the remaining ovary was removed. Ovaries were examined for the presence of an oocyte within the follicle. RESULTS: Monkeys had the expected levels of changing reproductive hormones during Cycle 1. Meloxicam treatment in Cycle 2 did not alter hormone levels or the luteal phase length. Follicles of ovaries removed during Cycle 3 did not contain oocytes, indicating successful ovulation. Follicles did contain oocytes after meloxicam treatment beginning in the mid follicular (67%), late follicular (100%) or periovulatory (50%) phase of Cycle 4, indicating failure of ovulation. CONCLUSIONS: A 5-day course of oral meloxicam administered around the time of ovulation reduced the rate of oocyte release without alteration of reproductive hormones or menstrual cycle length. Meloxicam may be effective as an emergency contraceptive in women.

Family planning: today and in the future.

This review covers the state of contraceptive development noting new entries in the clinic (mainly steroidal and different delivery methods) and novel leads for nonsteroidal female- and male-methods in the pipeline. The time taken to market and the absence of partnerships with industry are stressed as major factors for the slow progress in their development.

Public-private partnerships advance contraceptive research and development.

The concept of public-private partnerships as a way to tackle global health problems is discussed. It is noted that surveys of such partnerships have not included contraception and contraceptive research and development (R&D), since pregnancy is not regarded as a disease. Nevertheless, there has been an attempt to apply the concept to improve maternal health through establishment of the Consortium for Industrial Collaboration in Contraceptive Research (CICCR) and its involvement with the AMPPA projects. The outcome of the CICCR initiative is discussed. Actions for the future are outlined.

Expression of leukemia inhibitory factor receptor and gp130 in mouse uterus during early pregnancy.

Leukemia inhibitory factor (LIF) is essential for implantation of mouse embryos. The aim of this study was to assess the expression and regulation of LIF receptor (LIFR) and gp130 mRNA in mouse uterus during early pregnancy using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). A strong level of LIFR mRNA signal was detected in the luminal epithelium on day 5 of pregnancy. On day 6-8 of pregnancy, LIFR signal was mainly localized in the decidua. LIFR signal in the luminal epithelium of ovariectomized mouse was slightly stimulated by a combination of progesterone and estrogen. By RT-PCR, LIFR mRNA signal was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 5. A low level of gp130 mRNA signal was seen in the glandular epithelium on day 3 of pregnancy and reached a high level on day 4 of pregnancy. gp130 signal in the decidua appeared on day 6 of pregnancy and reached a high level on day 7 and 8 of pregnancy. After the ovariectomized mouse was treated with a combination of progesterone and estrogen, a strong gp130 signal was observed in the glandular epithelium, while no signal was detected after progesterone or estrogen treatment alone. By RT-PCR analysis, gp130 mRNA was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 4 of pregnancy. Additionally, a high level of LIFR and gp130 mRNA signal was detected in the decidua under artificial decidualization compared to the control uninjected horn. The co-expression of a high level of LIFR and gp130 mRNA in the decidua may play a key role during the decidualization and placentation.