Paula Briggs

Early Pregnancy Loss and Ectopic Pregnancy

First trimester pregnancy loss is usually called a “miscarriage”. However “early pregnancy loss”(EPL) is all encompassing as it also includes ectopic pregnancy.

Impact of UK Medical Eligibility Criteria implementation on prescribing of combined hormonal contraceptives

Objectives Combined hormonal contraceptives (CHCs) are the most widely prescribed contraceptive methods in the UK; however, their use is associated with significant cardiovascular risk for women with some medical conditions and risk factors. The objective of this study was to assess the potential change in CHC prescribing among higher-risk women following publication of the UK Medical Eligibility Criteria for Contraceptive Use (UKMEC) in 2006. Methods A cross-sectional study was conducted using the General Practice Research Database to analyse UK women aged 15–49 years who were prescribed CHCs during the period 2004–2010. Of women prescribed CHCs, those at higher risk of cardiovascular events (with UKMEC Category 3 or 4 risk factors) were identified. The percentage of higher-risk CHC users, among all CHC users, in 2005 (pre-UKMEC) was compared to that in 2010 (post-UKMEC). Results The percentage of higher-risk CHC users significantly decreased by 0.8% (95% CI 0.68% to 1.02%) following publication of UKMEC [8.1% (95% CI 7.98% to 8.22%) in 2005 vs 7.3% (95% CI 7.14% to 7.38%) in 2010; p<0.001]. However, an estimated 1 74 472 women in the UK were prescribed CHCs in 2010 despite having Category 3 or 4 risk factors. The most common Category 3 or 4 risk factors were body mass index ≥35 kg/m2, hypertension and smoking in women aged ≥35 years. Conclusions Despite the observed reduction in prescribing of CHCs to higher-risk women after publication of UKMEC, a large number of women with Category 3 or 4 risk factors are still prescribed CHCs. The increased risk of cardiovascular events is unnecessary for many of these women given the availability of alternative contraceptive methods.

Continuation rates bleeding profile acceptability and satisfaction of women using an oral contraceptive pill containing estradiol valerate and dienogest versus a progestogen-only pill after switching from an ethinylestradiol-containing pill in a real-life setting: results of the CONTENT study.

Background Oral contraceptives are still associated with high discontinuation rates, despite their efficacy. There is a wide choice of oral contraceptives available, and the aim of this study was to assess continuation rates, bleeding profile acceptability, and the satisfaction of women in the first year of using a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) versus a progestogen-only pill (POP) in a real-life setting after discontinuing an ethinylestradiol-containing pill. Methods and results In this prospective, noninterventional, observational study, 3,152 patients were included for the efficacy analyses (n=2,558 women in the E2V/DNG group and n=592 in the POP group (two patients fulfilled the criteria of the efficacy population, but the used product was not known). Women had been taking an ethinylestradiol-containing pill ≥3 months before deciding to switch to the E2V/DNG pill or a POP. Overall, 19.8% (n=506) of E2V/DNG users and 25.8% (n=153) of POP users discontinued their prescribed pill. The median time to discontinuation was 157.0 days and 127.5 days, respectively. Time to discontinuation due to bleeding (P<0.0001) or other reasons (P=0.022) was significantly longer in the E2V/DNG group versus the POP group. The E2V/DNG pill was also associated with shorter (48.7% vs 44.1%), lighter (54% vs 46.1%), and less painful bleeding (91.1% vs 73.7%) and greater user satisfaction (80.7% vs 64.6%) than POP use, within 3–5 months after switch. Conclusion The E2V/DNG pill was associated with higher rates of continuation, bleeding profile acceptability, and user satisfaction than POP use and may be an alternative option for women who are dissatisfied with their current pill.

Hormone replacement therapy and cancer

Sex steroids are not known to damage DNA directly. They can stimulate or inhibit cell proliferation, and thus can modulate tumor developmental progression. Sex steroid-related tumors in women are represented by breast cancer and endometrial cancer, and a possible relationship exists between sex steroids and both ovarian and colon cancer. Among current ERT users or those who stopped use 1-4 years previously, the relative risk of having breast cancer diagnosed increases by a factor of 1.023 for each year of hormone use. This increase is comparable with the effect on breast cancer of delaying menopause, and seems to be largely limited to lean women. The breast cancers diagnosed during ERT are more likely to contain ER and are less aggressive. Some reports indicate no increase in breast cancer mortality in HRT users. Recent data suggest that an estrogen-progestin regimen may increase breast cancer risk beyond that associated with estrogen alone. However, the effect of progestogens on the breast awaits further clarification. ERT/HRT is generally considered to be contraindicated in breast cancer patients, as no firm data are yet available from randomized clinical trials. Despite the potential risks, ERT/HRT could be considered for breast cancer patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given, particularly in women with ER-(hormone-resistant) cancers. Unopposed estrogen therapy is known to increase endometrial cancer risk, and is appropriate only for hysterectomized women. To negate the excess risk of endometrial hyperstimulation, an adequate progestin dose must be given in a continuous combined regimen or for an appropriate number of days in sequential regimens (10 days or more for some progestogens or 12 days or more for other progestogens). An appropriate combination of estrogen and progestin does not appear to increase, and may even decrease, the risk of endometrial cancer. HRT is generally considered to be contraindicated in endometrial cancer patients. Despite the potential risks, HRT could be considered for patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given. Available data suggest a reduced risk of colorectal adenoma and colon cancer in current users of HRT, but definitive studies are still needed. There is no contraindication to HRT prescription in colon cancer survivors. Consistent epidemiological data describe a decreased incidence of ovarian cancer with oral contraceptive use during the reproductive years. Studies on HRT and risk of epithelial ovarian cancer have produced conflicting results but most data seem to exclude a strong association. While no data contraindicate HRT use in epithelial ovarian cancer survivors, current studies do not allow us to exclude the possibility that estrogens alone could stimulate ovarian cancer growth in a small fraction of patients. Additional studies are required. It is important to consider that not all estrogens and progestins are used with the same dosage, route of administration (oral, transdermal and for estradiol intranasal) and, mostly, different estrogens do not show the same bioavailability and tissue effects. The available data do not allow to discriminate for all these variables and therefore it is inappropriate to consider jointly all forms of hormonal therapy. This issue is considered as an important area for future evaluation and research. The International Menopause Society is in the process of drawing up specific recommendations for further research in the field of HRT and cancer.

Basic Embryology: The Development of the Foetus

With the joining of the oocyte and the sperm an embryo is created (Fig. 2.1). As both the oocyte and the sperm (gametes) contribute 23 chromosomes (haploid), the embryo now is made up of 23 pairs of chromosomes (46). The developing embryo inherits half its genetic material from each of its parents, thus it is diploid, and its genetic makeup is determined for life. As the cells continue to divide rapidly, each nucleus contains an identical chromosomal template. By the time it reaches the uterine cavity, the embryo has developed to the blastocyst stage (Fig. 2.2). The blastocyst differentiates into outer cells, the trophoectoderm or trophoblast, which will form the placenta as it combines with the uterine endometrium, and inner cells which form the inner cell mass (Fig. 2.3). These will form the embryo, as well as the amnion and yolk sac. This is the stage at which the process of implantation commences. By the eighth day, the cells of the inner cell mass proliferate into a rounded bilaminar structure. The embryo will develop from, this and a small slit like space forms to become the amniotic cavity. The ectoderm develops from the floor of this cavity and makes up one of the layers of the bilaminar embryonic disc, the other layer being the endoderm. The mesoderm develops as a further layer between the ectoderm and endoderm. As it grows outwards, in combination with the trophoblast, the chorion is formed. The cells continuous with the endoderm extend along the inner aspect of the blastocyst producing another fluid filled sac – the primary yolk sac. Ultimately the ectoderm will form the skin, nervous system and parts of the eyes, ears and nose. The endoderm is the origin of the linings of the gut and respiratory system, whereas the mesoderm is the origin of muscle, bone, blood tissues and connective tissue.

The Gynaecological History and Examination

Whilst a gynaecological consultation is a specialist referral, it is important to consider the patient as a whole, and to have an overall understanding of her medical history. Therefore a general medical history should be obtained, followed by a gynaecological history.

The Obstetric History and Examination

When taking an obstetric history, commence with the gynaecological history, as described in Chap. 4. Then expand on the details of pregnancies and confinements.

Infections During Pregnancy – Varicella, Herpes, Cytomegalovirus, Toxoplasma, Listeria, Group B Streptococcus

Varicella Zoster Virus (VZV) is a DNA virus of the herpes family. Infection results in a vesicular eruption of the skin.

Basic Physiology: The Menstrual Cycle

Understanding menstrual physiology is the basis for understanding the whole concept of fertility including the mechanism of action of contraception. It is also the basis for natural family planning.

Managing the menopause: 21st century solutions

This is a truly international collaboration with contributions from experts from all over the world. The book aims to clarify much of the confusion produced by publication of data from the Women’s Health Initiative (WHI) and the Million Women Study (MWS). These have left many health care professionals confused and reluctant to prescribe hormones or even to discuss management options for women going through the menopause. This has resulted in many women being denied treatment or discontinuing their treatment unnecessarily. The book begins with good clear explanations of the physiology of the menstrual cycle and menopause and predicting ovarian reserve. I found the information on anti-Mullarian hormone for predicting ovarian reserve interesting, particularly after chemotherapy in a paediatric oncology context. Also there is a review of the latest evidence around cryopreservation of ovarian tissue before treatment in young women. There is an excellent overview of the history and politics of the menopause and a useful review of the whole saga of WHI, putting the outcomes into perspective. The chapters on diagnosis of menopause with assessment of symptoms rather than measurement of hormone profiles for the vast majority of menopausal women, explanation of the risks and benefits of hormone replacement therapy, and managing symptoms with non-hormonal alternatives are all very useful and practical. Other sections of the book review the evidence around cardiovascular disease, osteoporosis, venous thrombosis and cancers, and put the research into perspective with clear guidance on how to explain the risks and benefits and compare the advantages and disadvantages of the different management options. There are sections on sexual function, contraception and vulvovaginal atrophy. These are areas often neglected by health care professionals but which can be very significant for women. I particularly like the case studies focusing on common menopause presentations that precede, and are subsequently discussed in, many of the chapters. This book is very broad in scope and covers all aspects of menopause in women. It deals with the latest research and puts this into perspective, making this book a very useful resource for all those involved in the care of women going through the menopause. The final chapter on male menopause is perhaps a slightly surprising addition but makes for interesting reading. Overall this is a very useful book and a good reference source.