Conditions affecting female fertility

Age

It is well recognised that a woman at some time in her life will find that her periods stop.  This usually happens in her late 40s or early 50s (average about 52).  The reason is that she has used up all her follicles in her ovaries.  No longer can she produce estrogen, nor can she produce eggs.  It seems that the best follicles are used first and so, for some time (years) before the last period, there may be irregular periods, symptoms of estrogen lack, difficulty in conception and problems with a pregnancy if it does occur.

Individuals vs. Populations

Every individual and couple is unique and could be more fertile or less fertile as compared to the average for their age. Some 30 year olds already have significant egg quality and/or quantity issues and some 43 year olds are still fertile.
There are also no guarantees that an individual woman will have a smooth drop in her fertility potential as she ages. Although rare, it is possible to have a rapid decline in egg quantity and quality as early as the teens or twenties.

Female Age - Egg Issues
  • - Successful pregnancy outcome is very much related to female age - when using the woman's own eggs.
  • - When donor eggs are being used, the age of the egg donor is the important issue.
  • - With egg donation, the age of the recipient woman has very little impact on the chance for successful pregnancy.
  • - Therefore, the age of the egg is very important, but the age of the uterus is not.
  • - Much of the problem is due to an increased percentage of chromosomally abnormal eggs with aging

Can we measure the effect of age?
In general, women do not seek to get pregnant every month of their adult life. So it is difficult to get meaningful figures. However, in 1957 Tietze published a useful estimate. The study was on a large population that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. Infertility rates are now higher in the general population than for the population in this study from the 1950s. This study found: By age 30, 7% of couples were infertile By age 35, 11% of couples were infertile By age 40, 33% of couples were infertile At age 45, 87% of couples were infertile

What is Premature Ovarian Failure (POF)?

Premature Ovarian Failure (POF), also known as Primary Ovarian Insufficiency (POI) or early menopause, is a loss of ovarian function before the age of 40. POF can affect women at various ages from teenage years to thirties. Women with POF are at a greater risk of a range of health issues, including osteoporosis, estrogen deficiency (hot flushes, vaginal dryness, etc.) and heart diseases. These POF-related issues can usually be managed well with hormonal replacement (HRT). However, in an infertility context, POF poses a challenge, as the loss of ovarian function means that the probability of pregnancy in women with POF is greatly reduced.

Diagnosis of premature ovarian failure (POF)
Even if you have been told that you have POF, it may be too soon to despair. Quite often, we are surprised who is diagnosed with POF. Many patients with a supposed diagnosis of POF actually don't really suffer from POF. Many "POF" patients, when tested, turn out to suffer from premature ovarian aging (POA), not POF.
While these two conditions sound similar, correct distinction between POF and POA is crucial. Women with POA can get pregnant.  Those with POF are extremely unlikely to do so.
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Distinction between POF and POA
The distinction between POA and POF is not difficult. It is based on the maximum level of follicle-stimulating hormone (FSH). Patients with FSH levels above 40.0mIU/mL, a post-menopausal level, are diagnosed with POF, while patients with elevated FSH levels> that do not exceed this threshold are diagnosed with POA.  POA may also be assessed with an AMH blood test.  (Contact the office at 0845 6861540 to arrange a test)

Causes of premature ovarian failure
There are several known causes for premature ovarian failure, amongst them genetic conditions that affect the X chromosome, such as Turner Syndrome and Fragile X syndrome. Autoimmunity (immunity against oneself) has also been implicated. In addition, surgical loss of excessive ovarian tissue (for example, after surgery for endometriomas, also called "chocolate cysts") can put the patient into early menopause. Chemotherapy and radiation can also cause premature ovarian failure.

Getting pregnant with premature ovarian failure (POF)
As already noted above, even in the best of hands, pregnancy in women with POF is a rare event, and most will end up having to use egg donation.

What are Refractory ovaries?
Rarely, we find women who have a high FSH level, indicating that the ovaries do not respond to normal stimulation.  On looking at a biopsy of the ovary, we find plenty of follicles.  It is not known why this happens.  Sometimes it resolves spontaneously and sometimes with more stimulation.  However it is difficult to predict what will happen.

Diabetes

Abnormal insulin function, whether insulin resistance or diabetes, impacts upon fertility.  Type 1 Diabetes used to be called “Juvenile” as it tends to start early in life.  However it may be a long time before it is diagnosed.
A recent paper from Chile shows a clear relationship between fertility and accurate management of insulin therapy.   

(Codner et al.   Fertil Steril    Volume 95, Issue 1 , Pages 197-202.e1, January 2011 )       

Most of the Type 2 diabetes female patients are postmenopausal women, but with changing dietary and lifestyle patterns, the prevalence of obesity is increasing, thus raising the incidence of Type 2 diabetes during the reproductive years.  This is very closely linked to PCOS.
Added to the increased incidence of subfertility amongst diabetic patients is an increased rate of miscarriage, of fetal malformation, macrosomia (big babies) and other complications of pregnancy.

Thyroid disease

Abnormal thyroid function has long been known to affect a woman’s periods, slight aberration leading to heavy or irregular periods and severe disease leading to amenorrhoea.  It is not surprising, therefore, that it impacts upon her fertility.  There is seldom a problem with fertility but careful management is necessary during pregnancy. 

What is PolyCystic ovarian syndrome? (PCOS)


A syndrome is a collection of symptoms and signs that appear together. Usually when we talk of a syndrome, it is because we do not know the actual disease process that produces the symptoms. So it is with PCOS. PCOS is not just about the ovaries, it is a "whole body disease"
It would seem to affect, to some extent, perhaps 30% of the female population of child bearing age.
We know that it is a disorder of the normal control of the menstrual cycle. The Pituitary gland instructs the ovaries to ovulate (release the egg) and then to produce the hormone progesterone with the release of a burst of luteinising hormone (LH) in the normal cycle but in this condition, the circulating LH is high throughout the month. It seems that the ovary is unable to respond by producing progesterone and instead produces hormones that are related to progesterone but act much more like androgens (male hormones). These produce many of the distressing symptoms.
Excess fat could be caused by these hormones which are like the anabolic steroids used by body builders. However, obesity could be a cause of the problem as it counteracts the action of insulin (insulin resistance). This leads to excess production of insulin by the body. Also there is a reduction in sex hormone binding globulin (SHBG). This will usually bind the small quantities of testosterone (male hormone) in the blood rendering the bound portion inactive. A reduction in SHBG, therefore, makes more testosterone active.
The lack of progesterone is recognised by the brain which instructs the pituitary gland to produce more LH and so a vicious cycle is set up.
The incorrect instructions to the ovarian follicles means that they do not develop to the stage of producing an egg (or is it their inability to develop properly that is the cause of all this? We do not know). The arrested follicles take up a position just under the surface of the ovary giving rise to the name of the syndrome and a particular picture on ultrasound examination.There is also a thickened capsule to the ovary.

How does PCOS present to us in the clinic?

Most commonly, PCOS is found in my subfertility clinic. Women who have none of the gross symptoms or signs of PCOS, are found on investigation to have a raised LH (on more than one occasion in a cycle) and a typical ultrasound picture.
Secondly, irregular or absent periods in women who are not seeking a pregnancy may lead to this diagnosis.
Rarely, women attend simply because of facial hair growth. Although many cases are due to a racial variant of normal, it is distressing that they have often spent many years and many pounds relying on cosmetics without a diagnosis.
The extreme presentation of a fat hairy woman with absent periods and huge polycystic ovaries as described by Stein and Leventhal in the 1930s is very rare.

How can we treat PCOS?
The treatment depends very much upon the distressing symptom and the desires of the woman for pregnancy.
Cosmetic approach: Weight loss is vital and may be all that is necessary for normal ovulation to resume. It might be helpful, for those who are unable to lose weight by diet and exercise, to take a course of a drug such as Xenical (Roche Ltd) which interferes with fat absorption or Reductil (Abbott Labs).
Electrolysis, laser treatment and depilatory creams are often used to reduce facial hair. Recently, a new cream has been licensed for this purpose. Vaniqa (eflornithine 11.5% cream, Shire Pharmaceuticals Ltd.) is not an anti-androgen but slows hair growth in the area to which it is applied. It should not be used before proper investigation of the reason for the hirsutism.
Anti-androgen drugs: The oral contraceptive pill Dianette contains the anti-androgen cyproterone acetate and is the treatment of first choice for a woman with androgenic symptoms (eg. acne or hirsutism) and who does not wish to conceive. (Other drugs which may sometimes be used include: cyproterone in higher dose, spironolactone, flutamide or finasteride. none of these is actually licensed for use in PCO.)
Fertility drugs: Clomifene citrate is usually the first line of treatment for those seeking a pregnancy. More complicated fertility treatment may be appropriate for some women.
Drugs affecting insulin resistance: Metformin is used for non-insulin dependent diabetics. It is being used more and more for obese women with PCOS to reduce the insulin resistance.
Surgical treatment:  Wedge resection of the ovary has been found to be helpful. However this is an open operation and risks adhesion formation. We, therefore, usually drill a series of holes in the ovarian capsule at laparoscopy. This may allow normal ovulation or permit a greater response to a lower dose of clomifene.

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