Vikram Sinai Talaulikar

Ulipristal acetate: a novel option for the medical management of symptomatic uterine fibroids.

Fibroids, the most common tumor in women of reproductive age, impact negatively on women’s health and quality of life, and have significant cost implications for their management. The current mainstay treatments are surgical (myomectomy and hysterectomy) and more recently radiological (UAE and focused ultrasound surgery). Hysterectomy is curative but precludes future fertility, whereas the impact of the other treatments on reproduction is uncertain. With women in Western societies deferring childbearing to their 30s and 40s, when fibroids are most symptomatic, there is a pressing need for a uterus-sparing medical therapy that is cheap, effective, and enhances reproductive potential. Serendipity and meticulous translational research has shown that progesterone augments fibroid proliferation, raising the possibility that progesterone receptor modulators could inhibit fibroid growth; this research has culminated in the emergence of ulipristal acetate (UA), a first-in-class, oral selective progesterone receptor modulator (SPRM) that has successfully completed phase III clinical trials. It has been licensed in Western Europe for short-term clinical use prior to surgery, and has shown efficacy with a significant reduction in uterine bleeding, fibroid volume, and improved quality of life, without the side effects associated with other medications such as gonadotropin-releasing hormone (GnRH) agonists. As with all new medicines, there are concerns surrounding UA, not least its effect on the endometrium and the long-term impact on general health and reproduction. Research to date has tended to be industry led, and therefore, there is a need for researcher/clinician-led studies to address the wider issues concerning SPRMs. UA may not turn out to be the “Holy Grail” of medical therapy in the treatment of symptomatic uterine fibroids, but it has rightly given cause for a huge optimism. Further laboratory and clinical research into PRMs and related compounds will no doubt lead to more refined medications.

Folic acid in obstetric practice: a review.

Folic acid is one of the B complex vitamins and is now recognized as a major component of the periconceptional care of women in the reproductive age group. Deficiency of folic acid can lead to neural tube defects in the fetus and megaloblastic anemia in the mother. Due to its lower bioavailability from natural foods, many countries have adopted mandatory folic acid food fortification programs. Although these programs have been a public health triumph in reducing the burden of neural tube defects, there have been growing concerns about the role played by folic acid supplementation in the rising colon cancer rates over the past decade. The majority of the evidence available to date is reassuring, and until further long-term population as well as laboratory studies are completed, folic acid will continue to play a vital role in early pregnancy care. It is important for healthcare professionals to be aware of the recent evidence that has accumulated, suggesting higher folic acid requirements in certain groups of women and offer correct advice on the use of folic acid supplements. This review looks at some of the existing evidence on folic acid supplementation and summarizes the recommendations on the use of folic acid supplements by obstetricians, family physicians, and others providing prenatal care. Target Audience: Obstetricians and Gynecologists, Family physicians Learning Objectives: After completing this CME activity, physicians should be better able to evaluate the need for folic acid supplementation in various patient groups to lower the risk of neural tube defects due to folate deficiency; recommend common, natural and fortified food sources rich in folic acid; and distinguish the effects of folate deficiency in the mother and fetus.

Reproductive outcomes after assisted conception.

The last three decades have witnessed a dramatic increase in the use of assisted reproductive technology (ART) so that now, in developed countries, 1.7% to 4.0% of all children are born after ART. Although absolute risks appear small, data from prospective and retrospective studies indicate increased risks of adverse maternal and perinatal outcomes after ART as compared with spontaneous conception. Recent studies suggest that underlying maternal factors and subfertility play an important role in some of these outcomes rather than the ART procedure itself. A significant risk of assisted conception is multiple pregnancies, but even singleton pregnancies achieved by ART are at a higher risk of hypertensive disease, diabetes, prematurity, low birth weight, and perinatal mortality even after adjusting for confounders. Couples undergoing ART procedures should be counseled in advance regarding increased risks of pregnancy complications and higher rates of obstetric interventions. Although conflicting data exist, studies of children born from ART suggest increased rates of congenital malformations, imprinting disorders (Beckwith-Wiedemann syndrome and Angelman syndrome), and marginally increased risk of cancer. However, the current evidence is inadequate, and prospective long-term studies are needed to eliminate the effect of confounders and draw definite conclusions about the long-term outcomes after ART. The absolute risk of imprinting disorders remains small, and routine screening is not recommended at present. The long-term outcomes after ART are difficult to evaluate because of the variability in ART methods and data reporting, and there is a need for standardized methodology for follow-up after ART.

Progesterone and progesterone receptor modulators in the management of symptomatic uterine fibroids.

The majority of symptomatic uterine fibroids are currently treated by surgical interventions (myomectomy or hysterectomy) or radiological treatments (uterine artery embolisation or focussed ultrasound surgery). None of these treatments is a panacea, and what is conspicuous is the lack of an effective long-term medical therapy for a disorder so common among women of reproductive age. It has been known for some time that progesterone and its receptors enhance proliferative activity in fibroids and this has raised the possibility that anti-progestins and (PRMs) could be useful in the medical management of fibroids. Some of the compounds which have produced promising results in recent clinical trials or research studies include mifepristone, CDB-4124 (telapristone), CP-8947, J-867 (asoprisnil) and CDB-2914 (ulipristal acetate or UA). UA has recently completed Phase III clinical trials with very encouraging results, and has now acquired a licence for clinical use in Europe. While considerable research has yet to be done on the long-term safety and efficacy of UA there is nevertheless good reason for optimism on the emergence of effective medical therapy in the form of UA and possibly other PRMs.

Maternal, perinatal and long-term outcomes after assisted reproductive techniques (ART): implications for clinical practice

The use of assisted reproductive techniques (ART) is on the rise throughout the world and the number of babies born as a result of ART has reached an estimated total of 5 million since the worlds first, Louise Brown, was born in 1978. Data from many prospective and retrospective studies have suggested increased risks of adverse maternal, perinatal and long-term outcomes after ART compared to natural conception. Recent research suggests that underlying maternal factors rather than ART methods themselves play a significant role in causing such outcomes. Couples attempting ART need to be provided with accurate and reliable information on risks of adverse reproductive outcomes and reassured that absolute risks appear small. Clinicians need to remain vigilant about increased risk of pregnancy complications and formulate a plan of care for the woman, from periconception to the puerperium, which aims to prevent or minimise maternal and perinatal morbidity. This review attempts to summarise the available data on reproductive outcomes after ART and provide guidance to the obstetricians and primary care physicians about management of ART pregnancies.

Exploiting the antioxidant potential of a common vitamin: Could vitamin C prevent postmenopausal osteoporosis?

Aim:  Oxidative stress is thought to play a central role in the pathophysiology of various conditions affecting womens health, including cancer, preeclampsia and osteoporosis. On the back of animal experimentation, we sought to establish whether the oral administration of vitamin C at high doses to postmenopausal women would achieve the plasma antioxidant activity that could prevent osteoporosis.

Failed induction of labor: strategies to improve the success rates.

The rates of induction of labor (IOL) are rising all over the world. In developed countries, one of every 4 babies is born after IOL at term. The recent World Health Organization guidelines on IOL recommend that failure of induction does not necessitate cesarean delivery [WHO recommendations for induction of labor. World Health Organization, 2011]. These guidelines come when there are concerns that failed primary inductions in nulliparous women, which have led to escalation of the cesarean delivery rates. Obstetricians must recognize the risks associated with IOL (including failure and need for cesarean delivery) and avoid inductions for borderline indications, which are not evidence based. The issue of “failed induction of labor” is topical, and there is a need to define this entity and offer alternatives to cesarean delivery in the management of this group of women. Research is required to develop a test to accurately identify those fetuses most at risk of morbidity or stillbirth who would truly benefit from an early IOL and assess the cost-effectiveness of policies of routine IOL. In this review, we summarized the current recommendations for best practice in the area of IOL, defined “failed induction,” and described options to improve the success rate after “failed primary induction of labor.” Target Audience: Obstetricians & Gynecologists and Family Physicians Learning Objectives: After the completing the CME activity, physicians should be better able to classify the factors determining success or failure of induction of labor, counsel women about risks and benefits of various methods of induction of labor, and compare the options of management available after failed primary induction of labor.

Variation in antral follicle counts at different times in the menstrual cycle: does it matter?

Antral follicle count (AFC) variation was examined across the menstural cycle and its effect on clinical management assessed. In 79 women, AFC was documented in early (iAFC) and late follicular phase (sAFC). Absolute agreement between iAFC and sAFC and agreement for classification into categories of risk of extremes of ovarian response were examined. Ovarian stimulation protocols designed with iAFC and sAFC, and the predictive value of iAFC and sAFC for extremes of ovarian response, were compared in women undergoing ovarian stimulation. Significant differences were found between iAFC and sAFC (16 [IQR 9-24] versus 13 [IQR 7- 21]; P = 0.001), with moderate agreement for the classification into at risk of extremes of response (k = 0.525). Agreement for protocol selection based on either AFC (k = 0.750) and starting gonadotrophin dose was good (concordance correlation coefficient 0.970 [95% CI 0.951 to 0.982]). Predictive value for iAFC and sAFC was maintained for poor ovarian response and risk of ovarian hyperstimulation syndrome (OR 0.634 [0.427 to 0.920], 0.467 [0.233 to 0.935]) and (OR 1.049 [0.974 to 1.131], 1.140 [1.011 to 1.285]). Across the cycle, AFC varies but does not significantly affect ovarian stimulation protocol design and prediction of extreme ovarian response.

Low participation rates amongst Asian women: implications for research in reproductive medicine

The last two decades have witnessed tremendous advances in the field of reproductive medicine, especially assisted reproductive technology and stem cell research. As research continues in future, it is vital to ensure that individuals from all ethnic backgrounds are represented in the study populations so that the findings of the research can be generalised for the benefit of all. Many studies, however, have noted a trend of low participation rates amongst Asian women in reproductive research. Inequalities in the ethnicity of research participants can be a source of substantial bias, and have major ethical and scientific ramifications. Several factors such as educational status, fear of wrong-doing, communication barriers, and socio-cultural beliefs have been suggested to play a role. There is a need for further exploration of the factors influencing Asian womens decision to accept or decline participation in reproductive research and for development of effective targeted strategies for research recruitment with the aim of encouraging research participation as well as donation of cryopreserved embryos or other reproductive tissues.

Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: implications for trophoblastic invasion of the placental bed.

The human embryo–maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis.