There is ample evidence from animal and human observations that extremes of body weight influence reproductive processes. Women who are under a certain weight or body mass index are less likely to cycle regularly, have more difficulty in getting pregnant and have smaller babies. Those who are overweight also suffer serious reproductive problems in that they have a greater risk of oligo- or amenorrhoea, infertility and gestational diabetes. Several large epidemiological studies indicate that reproduction is adversely affected by excess weight. Two of the largest studies (Nurses' Health Study and the British Birth Cohort Study) that convincingly show that being overweight impairs menstrual and fertility function indicate that the greater the body weight and body mass index (BMI), the more significant the effect. Being overweight in adolescence appears to affect reproductive function later in life.

The ovarian hyperstimulation syndrome (OHSS) remains one of the enigmas of reproductive medicine. We all fear its development in our patients and we all have “pet” policies for its prevention and treatment. Despite this, its incidence has not changed significantly in the last 20 years with the severe form still occurring in 0.3–5.0% of cycles. Its pathogenesis clearly has a physiological basis but it would appear to be compounded by the body's homeostatic response to the changes produced by the syndrome.

Decidual cells prevent peri-implantational endometrical bleeding

During the menstrual cycle, the concerted effects of estradiol (E2) and progesterone induce human endometrial stromal cells (HESCs) to undergo decidualization, the collection of morphological, proliferative and biochemical changes that transforms stromal cells to decidual cells. In the luteal phase, progesterone initiates E2-primed HESCs to decidualize around blood vessels. Under continued progesterone stimulation, decidualization spreads throughout the late luteal phase and gestational endometrium. Among species with a haemochorial placenta, human trophoblasts are the most intrinsically invasive and human endometrium undergoes the most extensive decidualization reaction. Implanting blastocyst-derived syncytiotrophoblasts breach endometrial blood vessels embedded in a matrix of decidual cells. This invasive process institutes the primordial uteroplacental circulation, and provides the embryo with oxygen and nutrients. That it risks bleeding is clear from the phenomenon of chemical pregnancy, in which trophoblast-derived human chorionic gonadotrophin (hCG) appears transiently in the maternal blood followed by localized decidual bleeding. After endovascular invasion by syncytiotrophoblasts, extravillous cytotrophoblasts penetrate uterine spiral arteries and initiate the morphological changes that lead to increased intervillous blood flow. The occurrence of decidual haemorrhage during this period is associated with spontaneous abortion, abruption and preterm birth. Ectopic pregnancies are most frequently complicated by haemorrhage in primate species lacking a true decidua, thus underscoring the importance of decidual cells in preventing uterine bleeding.

Infertility, a failure of conception after at least 12 months of unprotected intercourse, will affect 14–17% of couples at some time in their reproductive lives. The types of infertility, with their respective frequencies, are tubal and pelvic pathology (35%), male problems (35%), anovulation (15%), unexplained infertility (10%) and other infrequent problems (5%). While anovulation, mild/moderate endometriosis, unexplained infertility and moderate oligozoospermia can be treated with mild ovarian stimulation and timed intercourse and/or intrauterine insemination (IUI), no treatment options are available for nonoperable tubal problems or treatment failures with IUI.

The term breakthrough bleeding (BTB) is rather poorly defined, but essentially describes the symptom of vaginal bleeding occurring with scheduled periods of withdrawal bleeding, in the absence of pelvic pathology in women taking exogenous sex steroids, usually contraceptives or hormone-replacement therapy (HRT). It may also describe occasional bleeding in those who are predominantly experiencing amenorrhoea due to these preparations. Rather confusingly, the term is sometimes used to describe intermenstrual bleeding in women who are not taking sex steroids, when structural or other pathological causes are more likely. In the absence of such pathology intermenstrual bleeding in the normal menstrual cycle is relatively uncommon, suggesting that exogenous sex steroids can profoundly disrupt the tight regulation of endometrial vascular development, function and breakdown. Intermenstrual bleeding also occurs spontaneously in some women and it is possible that this phenomenon has similar mechanisms to that seen in sex-steroid-related breakthrough bleeding.