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Female Infertility


The term infertility is defined as the inability to conceive despite regular and unprotected intercourse 1-2 years. However, risk factors such as the woman's age, abnormal menstrual periods, history of pelvic inflammatory disease and whether there has been previous abdominal or pelvic surgery, may warrant earlier investigations and treatment of infertility.

Endometriosis
Ovulation Problems
Tubal problems
Unexplained infertility
Age and infertility

Incidence of infertility
Infertility affects one in seven couples and affects both men and women.
It is important to remember that the majority of infertile couples can achieve a pregnancy and birth with treatment, they are subfertile. Only a minority of patients are sterile, i.e. even with treatment they would be unable to conceive. This could be due to no sperm, absent or non-functioning ovaries or an absent uterus.


Infertility is classified into two types:
Primary infertility if there was no previous pregnancy (approximately 40% of infertile couples).
Secondary infertility if there was a previous pregnancy whatever the outcome (approximately 60% of infertile couples).


Endometriosis
The term endometriosis refers to a benign and common disease in which cells like the ones that line the inside of the womb are established outside the womb e.g. on the ligament supporting the uterus in the ovaries, tubes, pelvis, bowels, bladder, etc. In patients with endometriosis, these cells, like the endometrium, respond to the monthly hormonal changes. When the woman with endometriosis menstruates, the endometrium is shed in the form of a period, the endometriosis breaks down in the same way but because these cells are trapped inside, and cannot escape, they form swellings filled with dark blood (known as chocolate cysts) and adhesions which may damage the tubes.

Endometriosis tends to occur in women who are in their 30s and early 40s, but occasionally occurs in those under 30 years of age.
Some patients with endometriosis may have no symptoms; some may experience considerable pain during their periods or during intercourse and their periods tend to be heavy.
On vaginal examination there may be tenderness and thickening of the supporting ligaments of the uterus in women with endometriosis. The majority of women with endometriosis are fertile. However, some women may experience difficulty becoming pregnant.


How does endometriosis cause infertility?
The anatomical distortion caused by endometriosis, especially when it is moderate and severe, could explain a mechanical cause of infertility, the precise mechanism by which minimal and mild endometriosis affect fertility is not fully understood. It is possible that endometriosis adversely affect the egg development, sperm binding to the egg, fertilization, tubal function and embryo implantation.

 

Diagnosis
The only means of diagnosis of endometriosis is by laparoscopy, which assesses the severity of endometriosis and the condition of the Fallopian tubes. There are a number of different classification systems for endometriosis, but the most widely used is that of the American Society for Reproductive medicine (ASRM) in which endometriosis is classified into four stages: minimal, mild, moderate and severe. There is little correlation between the severity of symptoms and extent of the endometriosis.
Ultrasound scans, CAT scans, or MRI scans, can identify cysts on the ovaries. However, these techniques cannot be used to make a definitive diagnosis of endometriosis.
Causes
Cause is unknown. However, the most widely accepted explanation for endometriosis is that viable cells from the lining of the womb pass upwards into the Fallopian tube and out into the pelvic cavity where they settle down. In most women these cells will be destroyed by the woman's immune system. However, in some women, these cells implant and proliferate, possibly due to a disorder of the woman's immune system.

Ovulation problems
This is the commonest cause of female infertility and it is also the one with the best chance of successful treatment. The woman usually presents with infrequent or very scanty periods, irregular periods or absent periods altogether (amenorrhoea). However, ovulation dysfunction can occur with apparently regular cycles. Sometimes women may notice an increase in body and facial hair, acne, milk secretion from her breasts etc.
Ovulation disorders can be classified into:
Annovulation i.e. lack of ovulation
Oligoovulation i.e. infrequent ovulation
Luteal phase defects

 

Causes
Primary
Here, the problem is in the ovary itself e.g.
The ovaries were surgically removed.
The ovaries were damaged by radiotherapy or chemotherapy treatment for cancer.
The ovaries only have a few eggs in them i.e. premature menopause which affects 1-2% of women below the age 40 years.
The woman was born without ovaries.
Ovulatory problems are the most common cause of female infertility and occur as a result of hormonal imbalance. This imbalance may arise either within the hypothalamus, the pituitary gland, or in the ovaries. Common causes of this include stress, weight loss or weight gain, excessive prolactin production (the hormone that stimulates milk production) and polycystic ovarian disease.

 

Polycystic Ovaries

About 20% of women have polycystic ovaries (PCO). This term describes the appearance, as seen on an ultrasound scan, of an increased number of small cysts on the surface of the ovary. Many women with PCO have normal regular cycles and have no problems conceiving.
However, some women with these ultrasound findings have a condition known as polycystic ovarian disease (PCOD). These women have a hormone imbalance with irregular or absent periods and they may have difficulty conceiving.

Treatment in the first instance usually involves the use of drugs to correct the hormone imbalance and to stimulate ovulation. If the woman is obese, weight loss may also improve the hormonal imbalance. Alternatively, a laparoscopy, ovarian drilling (making tiny holes on the surface of the ovaries using diathermy or laser) may be performed. In cases of PCOD these two modes of treatment may precede an IVF treatment cycle.

 

pco
Scan of pco ovaries

 

Secondary
Here, the ovaries are not the problem, but the lack of hormones released from the pituitary gland or hypothalamus. Causes include the following:
Severe stress.
Recent great gain or loss of weight.
Certain drugs.
Excess production of the hormone prolactin.
Disturbances involving the thyroid gland and the adrenal glands.
Some women have antibodies against sperm within their mucus and in these women, even at the time of ovulation, sperm are often unable to pass through the cervical canal. Hostile mucus may be bypassed by intra-uterine insemination (IUI) or IVF techniques.

 

Tubal problems
Tubal damage is a common cause of infertility. Damage to the fimbriae may reduce or stop their ability to pick up the egg and direct it into the Fallopian tube. Adhesions around the tube may distort the tube or reduce their mobility, thus affecting their ability to pick up the egg. Damage to the cells lining the tube may prevent sperm from reaching the egg or greatly reduce the chance of fertilization. Blockage of the tube can prevent the sperm from reaching the egg, or the fertilized egg from moving to the uterus and increases the incidence of ectopic pregnancy. Tubal blockage can be either proximal or distal. The former is where the blockage is located close to the uterus, while the latter is where it lies at the fimbriae.
Most women will not be aware of the tubal damage until they have been investigated for infertility. However, some may have severe period pains, irregular or heavy periods, chronic or recurrent pelvic pain and tenderness.

Causes
Infection
This is the commonest cause of tubal damage. Especially if the infection goes untreated or is treated inadequately at the time e.g.
Previous pelvic infection.
Sexually transmitted diseases such as chlamydia and gonorrhoea.
Spread of infection from internal organs such as appendicitis, bowel infection.
After an abortion, miscarriage or delivery, an infection may spread to the tubes.

Surgery
Any surgery that involves the Fallopian tubes, ovaries and uterus can cause adhesions. Sometimes abdominal surgery can also result in adhesions that may affect the tube.
Previous ectopic pregnancy
Previous ectopic pregnancies can be a cause of tubal damage.
Congenital abnormality
This is an abnormal development before birth such as an absent or mal developed tube.

Endometriosis
Endometriosis can lead to scarring of the tubes, adhesions, and in severe cases to blockage of the tubes.

Hydrosalpinx
Hydrosalpinx is a blocked, dilated, fluid filled Fallopian tube usually caused by a previous pelvic infection. In mild cases fertility may be restored by opening the tube surgically, otherwise IVF is the treatment of choice. There is some evidence that hydrosalpinx reduces the success rate of IVF and increases the risk of miscarriage. For this reason, some doctors may advice removing, or occluding the hydrosalpinx before the IVF treatment.

 

Unexplained infertility
Unexplained infertility affects 20-25% of infertile couples. In the majority of these cases, the failure to reach a diagnosis is not due to inadequate investigations, but is probably due to other factors, which cannot be assessed using conventional tests. For example, it is not currently possible to determine if the eggs are actually released at the time of supposed ovulation; if the fallopian tubes are able to pick up the eggs; if the sperm are capable of reaching the site of fertilisation; or if the eggs can be fertilised by the sperm.

In cases of unexplained infertility, assisted conception in the form of IVF is both diagnostic and therapeutic. For example, if the eggs are not released naturally, we release them by performing egg collection in both IVF and GIFT; if the tubes are not picking up the eggs, we bypass them when we perform IVF, if the sperm cannot reach the site of fertilisation, we overcome this by placing it with the eggs in fertilization procedures.
Finally, we can confirm fertilisation by IVF.


The relationship between age and fertility

Delayed child bearing is becoming increasingly common in western societies for several reasons: many couples prefer to rear their children only after establishing a stable relationship and financial security, also, there are increasing numbers of late and second marriages. Although pregnancies in women approaching 50 and beyond are occasionally reported, there is a decrease in fertility (the ability to achieve a pregnancy) with advancing age. The decline is gradual over the reproductive life span of the woman; it is particularly noticeable over the age of 30 and accelerates between 35 and 40 so that fertility is almost zero by the age 45.

The risk of miscarriage is also increased with ageing e.g. the risk of miscarriage at age 25-29 years is 10% while the risk at age 40-44 is 34%. Furthermore, advanced maternal age is associated within increased risk of chromosomally abnormal offspring.
Why does fertility decline with increasing age?
Ageing of the ovaries is the most prominent factor and is part of the normal ageing changes that affect all organs and tissues. Most women have about 300,000 eggs in their ovaries at puberty. For each egg that matures and is released (ovulated) during the menstrual cycle, at least 500 eggs do not mature and are absorbed by the body. By the time the woman reaches menopause which usually occurs between 50-55 years, there are only several thousands eggs remaining. As the woman ages, the remaining eggs in her ovaries also age, making them less capable of fertilization.
Fertilization is associated with a higher risk of genetic abnormalities e.g. chromosomal abnormalities such as Down syndrome with increasing age. The risk of a chromosomal abnormality in a woman age 20 years is 1/500 while the risk in woman age 45 is 1/20.
Gynaecological problems such as pelvic infection, tubal damage, endometriosis, fibroids, ovulation problems etc tends also to increase with age. As the woman gets older, she has more time to develop these conditions, which will adversely affect her fertility.
The effect of ageing in endometrial receptivity (ability of the endometrium to receive the embryo) is controversial. There is increasing evidence that the receptivity decreases with age.
Investigations of infertility in older women
It is advisable to seek the advice of your doctor/ specialist sooner than later so investigations and treatment can be started without undue delay.
Several tests may be useful in assessing the fertility potential in older woman e.g. blood tests to examine the levels of the hormones FSH, LH, oestradiol and inhibin on day 3 of your menstruation.
You will be more likely to be counselled about the risk of miscarriage and chromosomal abnormalities in relation to your age. In addition to the potential complications of pregnancy such as high blood pressure, bleeding and diabetes.
Treatment options for infertility in older women
There are limited options for treating older women who are menopausal or peri-menopausal. Older women usually respond poorly to ovarian stimulation and the live birth rates even with IVF treatment are significantly lower than with younger women. In addition, older are at increased risk of having medical problems in their pregnancies and deliveries. In order to improve the success rate of IVF treatment in older women, some clinics recommend assisted hatching, blastocyst embryo transfer, preimplantation diagnosis and only transfer normal embryos. Furthermore in some countries the transfer of high number of embryos is allowed.

One other option is  donor eggs.

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