Fertilization

 Normal fertility  is a complex process that first requires ovulation.  Ovulation is itself a complex process.  The sperm then need to make a perilous journey to reach the ovulated egg.  As soon as a single sperm enters the egg, fertilization occurs.  The fertilized egg must travel back down the fallopian tube and implant in the endometrium, 4-7 days later.  It then quickly grows into the wall of the uterus with rapid cell division from a single cell to a very recognizable fetus just a few weeks later.    

The normal cyclical changes in the endometrium and ovaries are a response to the cyclical change of hormones.  Therefore, the ovaries and endometrium are highly synchronized normally.  They may become unsynchronized in some situations.  

In the ovaries, a number of follicles develop but a dominant ovulatory follicle becomes apparent.  It becomes larger than the other follicles and usually ovulates by the time it reaches 18-30 mm in size.  A surge in LH production by the anterior pituitary gland at approximately day 14 of the menstrual cycle stimulates the release of an egg from the dominant follicle and the formation of the corpus luteum. 

On release of the egg, the ovulatory follicle becomes the corpus luteum. The corpus luteum  releases progesterone, which prepares the body for pregnancy.  

If the ovulated egg is fertilised and gives rise to an embryo, the cells that surround this early embryo (which are destined to form the placenta)  secrete human chorionic gonadotropin (HCG). This hormone has a very similar chemical structure to LH.  HCG can bind to and activate the same receptors as LH, and so maintains  the corpus luteum  which then continues to produce progesterone until the placenta is established.  

If progesterone is absent or levels are too low, irregular and heavy menstrual bleeding can occur. A drop in progesterone during pregnancy can result in a miscarriage and early labour. Mothers at risk of giving birth too soon can be given a synthetic form of progesterone to delay the onset of labour. 

Lack of progesterone in the bloodstream can mean the ovary has failed to release an egg at ovulation, as can occur in women with polycystic ovarian syndrome (PCOS). 

The corpus luteum shows typical features on ultrasound.   The corpus luteum is a thick walled cyst with characteristic "ring of fire" peripheral vascularity. It usually has a crenulated inner margin and internal echoes.  Identification of a corpus luteum is evidence that ovulation has occurred.  On the other hand, failure to demonstrate a corpus luteum suggests that ovulation has not occurred.   

Polycystic Ovarian syndrome (PCOS)

• PCOS is common, affecting at least 15% of women of reproductive age. 
• One of the central hallmarks of PCOS is an ultrasound scan showing typical findings of multiple small follicles, which can be termed polycystic ovarian morphology (PCOM)
• There is good evidence that many patients with PCOM but without clinical signs of PCOS are in a pre clinical phase. 
• PCOS precede serious medical complications including type 2 diabetes and cardiovascular disease. 
• Although there is no cure for PCOS, there is good evidence that early intervention with changes in diet and lifestyle can improve symptoms and help avoid some of the complications. 

• Address the underlying cause
• Although there is no cure for PCOS, there is good evidence that early intervention with changes in diet and lifestyle can improve symptoms and help avoid some of the complications.  
• Don't smoke
• Omega 3s   Fish oil has been associated with a long list of health benefits, and some research indicates that omega-3 supplements can decrease androgen levels in women with PCOS. One study found that women with PCOS who were given three grams of omega-3s a day for eight weeks had lower testosterone concentrations and were more likely to resume regular menses than subjects who received a placebo. 
• Vitamin Supplementation, especially Folate (pre conceptional) and
• Vitamin D long term (see below)
• Don't hesitate to seek expert help

Vitamin D

Evidence suggests that vitamin D modulates human reproductive processes.  Several observational studies reported a better in-vitro fertilization outcome in women with sufficient vitamin D levels (≥30 ng/ml), which was mainly attributed to vitamin D effects on the endometrium. One randomized controlled trial found an increased endometrial thickness in women with polycystic ovary syndrome (PCOS) receiving vitamin D during intrauterine insemination cycles. Further, vitamin D supplementation had a beneficial effect on serum lipids in PCOS women. Vitamin D treatment improved endometriosis in a rat model and increased vitamin D intake was related to a decreased risk of incident endometriosis. Vitamin D was also favorably associated with primary dysmenorrhea, uterine leiomyoma (fibroids), and ovarian reserve in late reproductive aged women.A number of studies also suggest that vitamin D is a powerful factor against fibroids, resulting in inhibition of tumor cell division and a significant reduction in its size, however, the exact role of this compound and its receptor in the pathophysiology of fibroids is not fully understood. 

In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥40 ng/ml) should be maintained. Vitamin D supplementation might improve metabolic parameters in women with PCOS. A high vitamin D intake might be protective against endometriosis and fibroids.

Vitamin D and pregnancy

Vitamin D has become increasingly recognized as a pluripotent regulator of biological functions above and beyond its classical effects on bone and calcium homeostasis. Expression of vitamin D receptor (VDR) for the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), as well as the 1α-hydroxylase enzyme that synthesizes 1,25(OH)2D (CYP27B1), has been reported for various tissues that can be broadly termed ‘barrier sites’, indicating that localized responses to vitamin D may be a key feature of these tissues. Prominent among these barrier sites is the placenta, acting as the interface between mother and fetus. Historically, the placenta was one of the first extra-renal tissues shown to be capable of synthesizing 1,25(OH)2D.   Initially, this was linked to the rise in maternal serum 1,25(OH)2D that occurs at the end of the first trimester of pregnancy. However, the presence of VDR in the placenta suggests that vitamin D functions in tissue-specific fashion at the fetal–maternal interface . One possible explanation is that 1,25(OH)2D acts as a regulator of placental calcium transport, but a placental immunomodulatory function has also been proposed. Moreover, the rapid induction of VDR and CYP27B1 early in pregnancy suggests that vitamin D may play a more fundamental role in the process of conception, implantation and development of the placenta itself. Thus, in addition to the active immune cell function classically observed in the maternal decidua, trophoblast cells also appear to make a major contribution to the regulation of placental inflammation.  The concept of vitamin D as a regulator of cellular motility and invasion is not novel and has been extensively reported in cancer states , where effects of vitamin D have been related to modulation of epithelial–mesenchymal transition (EMT) .    Vitamin D deficiency in pregnant women has been shown to be associated with increased risk for pregnancy complications . These include preeclampsia , fetal growth restriction, small-for-gestational-age fetus , bacterial vaginosis and gestational diabetes mellitus.  Maternal vitamin D deficiency has also been linked to adverse effects in offspring, including reduced bone density and childhood rickets, as well as increased risk of asthma and schizophrenia.  Low levels of vitamin D appear to contribute to the risk of autism, according to a study published in Molecular Psychiatry: According to the researchers, women with low vitamin D levels at 20 weeks of pregnancy are more likely to have children with symptoms of autism.  Children born to women who had low blood levels of vitamin D while pregnant more than double their risk of autism according to a study of more than 4,000 children in the Netherlands.  
 

 Uterine malformations result from abnormal development. Uterine 'duplication' actually occurs from incomplete fusion of the paired Mullerian ducts which normally occurs between the seventh and ninth weeks of gestation.   This results in a spectrum of abnormalities, depending on the degree of fusion.   Some uterine anomalies such as uterus didelphys have been associated with pain, infertility, miscarriage, preterm delivery and even endometriosis.  The good news is that despite the increased risk, most women with uterine abnormalities are able to become pregnancy and  carry healthy babies to term.