Gab Kovacs

Replacement of one selected embryo is just as successful as two embryo transfer, without the risk of twin pregnancy

The transition of in vitro fertilization from research to standard clinical practice has, to a great extent, been as a result of the use of controlled ovarian hyper stimulation. A disadvantage of the availability of multiple embryos has been the replacement of several embryos leading to an epidemic of multiple pregnancies. This retrospective review of 2606 fresh embryo transfers between 2001 and 2003, where either one or two selected embryos were replaced from an available cohort of at least four, shows that single embryo transfers have a similar pregnancy rate without the risk of multiple pregnancy.

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.

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.

Medical Conditions – Cardiac Disease, Thrombophilias, Rhesus Immunisation

This includes congenital cardiac abnormalities, rheumatic valvular heart disease, ischaemic heart disease, cardiomyopathy and pulmonary hypertension.

Termination of Pregnancy (TOP)

Therapeutic termination of pregnancy is defined as the use of an instrument or a hormone or chemical to abort a pregnancy. This is also known as a therapeutic abortion.