Infertility Information

 

Please find below a resource of information on Infertility.

In addition we recently published a 'Patient Guide to Infertility' This guide has been designed to provide practical information to couples contemplating fertility treatment so they can best make informed choices and decisions. This guide also assists referring doctors and clinics to supplement public information on infertility.

This booklet goes through the reasons for infertility and reviews the range of treatment options that are available to couples such as IVF and egg donation. There is also useful information on factors affecting the outcome of treatment and complications that can occur.

For a free copy of this booklet, please email us or call us on 01 299 3920

 

Introduction
Hostile Mucus
Age & Infertility
Treatment options for infertility in older women
Tubal disease and infertility
Endometriosis
PCOS

 

Introduction

Delayed child bearing is increasingly common in western societies for a number of reasons. These include the fact that many couples prefer to rear their children only after establishing a stable relationship and financial security. In addition, there are increasing numbers of late and second marriages. In Ireland, house prices have become so high that there is a need for both partners to work which may delay the time at which they start trying for a family.

Despite what you might think from the contemporary magazines (and the older mothers with small children that feature within their pages), 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. Bear this in mind when you next see some of the high profile older mums who feature regularly in celebrity magazines – they may well have been the recipient of donor eggs from a 22 year old college student.

The risk of miscarriage is also increased with age 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 also associated with an increased risk of congenital abnormality in the offspring.

Why does fertility decline with increasing age?

• Ageing of the ovaries 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 (usually 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 and their embryos less capable of implanting.
• Fertilisation is associated with a higher risk of genetic abnormalities e.g. chromosomal abnormalities. 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, and fibroids also tend to increase with age. Sexual function is also decreased with ageing e.g. libido, frequency of intercourse etc.
• Ageing does not just affect women, but also men to a much lesser degree. It affects sperm and coital frequency. However, there is no maximum age at which men are not capable of conceiving a child.
• Advanced maternal age also increases the risk of autosomal dominant diseases such as Marfan’s syndrome, neurofibromatosis and achondroplasia.
  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. (a) a blood test on the second or third day of your period to examine the levels of the hormones FSH, LH, estradiol and (b) an ultrasound scan of your ovaries.
• You will be more likely to be counselled about the risk of miscarriage and chromosomal abnormalities in relation to your age as well as the possible 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. Our pregnancy results for patients over 40 are detailed in the statistics section of this website. Other options of treatment include egg donation (using eggs donated by younger woman), embryo donation, or inter-country adoption.

Hostile Mucus

Cervical mucus

• Cervical mucus is a jelly-like substance produced by tiny glands in the cervix. It protects the womb by preventing bacteria from getting into the uterine cavity. The mucus changes during the menstrual cycle.
• During the first half of the cycle (before ovulation) mucus made by the cervical glands becomes watery and copious. Sperm can penetrate the watery mucus easily, and when intercourse takes place, they swim through it into the womb.
• After egg release (ovulation), the quality of the mucus changes because the ovary now starts to make the hormone progesterone. Mucus produced under the influence of progesterone is thicker, stickier and its quantity is reduced. Sperm cannot swim through this mucus, and it forms a barrier to sperm entry into the uterine cavity.
• Cervical Mucus/Sperm Interaction Tests
  The sperm normally travel through the cervical mucus to reach the uterus. Failure of passage through the cervical mucus is the primary cause of infertility for up to 10% of couples consulting for this condition.
• The post-coital test (PCT), first performed by James Marion Sims more than 125 years ago, has traditionally been a common way to determine cervical mucus/sperm interaction. It assesses sperm concentration and motility in a sample of mucus from the neck of the womb at mid-cycle (some hours after the couple have had sex). A normal PCT shows 20 or more spermatozoa per high-power field (when looking down the microscope). An abnormal test is usually due to intercourse occurring at the wrong time. Other causes also include anti-sperm antibodies, anovulation, an abnormal hormonal environment, female or male genital tract infections, poor sperm quality, and male sexual dysfunction (e.g. impotence). The value of this test is limited mainly because it relies on factors that which are beyond the control of the clinic. More specifically, a normal test is reassuring but the significance of an abnormal test is difficult to interpret.
• Tests that investigate the laboratory interaction between spermatozoa (sperm) and cervical mucus at mid-cycle can be clinically useful. These include crossed mucus-hostility assay (using donor spermatozoa and mucus as controls) as well those using bovine or human cervical mucus. However the clinical benefit of these tests is disputed - mainly because they assess a function of sperm which does not correlate closely with successful treatment (e.g. fertilization during IVF etc).
• Even if intercourse occurs at the most favourable time, less than 1 in every 2000 sperm will enter the mucus. These can survive for several days (unlike the rest which die because of the acid environment in the vagina). Once in the mucus, they steadily swim upwards into the womb over the next 2-3 days. Thus the cervical mucus acts as a reservoir bank to be drawn on if intercourse does not take place at ovulation. This is why you don't need to have sex everyday in order to conceive. The cervical mucus also acts as a filter - and allows only the best sperm to swim through it into the uterus and up towards the egg present in the fallopian tube.
• Mucus flows from the cervix down the walls of the vagina and is observed when it reaches the vulva. You can feel these changes by becoming aware of the wet feeling produced by the mucus and by observing it. This is very useful in allowing you to identify when you ovulate. You can chart what the mucus looks like and feels like each day from the day your bleeding stops. You will find the mucus present at your vaginal opening, i.e. the vulva. Remember, you do not need to feel inside the vagina because the vagina is always moist.
• Typically (in a 28-day menstrual cycle) at the end of bleeding you feel dry and no mucus is seen or felt. In some women, there is a small amount of mucus but it is usually thick and sticky. This is the infertile stage of dryness and lasts for two to three days.
• Once this is over, you may notice a feeling of moistness at the vulva and the mucus will change in appearance and feel. It becomes thinner, clearer, more profuse and stretchy, like the white of an egg. This fertile-type mucus produces a slippery wet lubricated feeling at the vulva. The last day when the mucus is stretchy or feels wet or vulva feels lubricated is the most fertile day of the cycle. It is important to realize that this is not when most mucus occurs but just the last day that the mucus has fertile characteristics. Ovulation usually occurs within one day of this and hence this is the best time to have intercourse in order to maximize your chances of conceiving naturally.

Age and infertility

Delayed child bearing is increasingly common in western societies for a number of reasons. Many couples prefer to rear their children only after establishing a stable relationship and financial security. In addition, there are increasing numbers of late and second marriages. In Ireland, house prices have become so high that there is a need for both partners to work which may delay the time at which they start trying for a family.

Despite what you might think from the contemporary magazines (and the older mothers with small children that feature within their pages), 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. Bear this in mind when you next see some of the high profile older mothers who feature regularly in celebrity magazines – they may well have been the recipient of donor eggs from a young college student.

The risk of miscarriage is also increased with age 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 also associated with an increased risk of congenital abnormality in the offspring.

Why does fertility decline with increasing age?

• Ageing of the ovaries is part of the normal ageing process that affects 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 (usually between 50-55 years) there are only several thousand eggs remaining. As the woman ages, the remaining eggs in her ovaries also age, making them less capable of fertilisation and their embryos less capable of implanting.
• Fertilisation is associated with a higher risk of genetic abnormalities e.g. chromosomal abnormalities. 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.
• Gynecological problems such as pelvic infection, tubal damage, endometriosis, and fibroids also tend to increase with age. Sexual function is also decreased with ageing e.g. libido, frequency of intercourse etc.
• Ageing affects women and, to a lesser extent, men. It affects sperm and coital frequency. However, there is no maximum age at which men are not capable of conceiving a child.
• Advanced maternal age also increases the risk of autosomal dominant diseases such as Marfan’s syndrome, neurofibromatosis and achondroplasia.
  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. (a) a blood test on the second or third day of your period to examine the levels of the hormones FSH, LH, estradiol and (b) an ultrasound scan of your ovaries.
• You will be more likely to be counselled about the risk of miscarriage and chromosomal abnormalities in relation to your age as well as the possible 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 are significantly lower than with younger women. Our pregnancy results for patients over 40 are detailed in the statistics section of this website. Other options of treatment include egg donation (using eggs donated by younger woman), embryo donation, or inter-country adoption.

Tubal disease and infertility

Tubal factor infertility accounts for up to one quarter of all cases of infertility. This includes cases where both the fallopian tubes are blocked, or one is blocked, or one (or both) are scarred. It is usually caused by pelvic infection (e.g. pelvic inflammatory disease (PID) or appendicitis), by pelvic endometriosis, or by scar tissue that forms after pelvic surgery.

In cases of relatively minor tubal damage it can be difficult to be certain if it is solely responsible for the infertility – or simply an additional factor in addition to other significant contributing causes. From a practical point of view, the presumptive diagnosis is of tubal factor unless the degree of scarring is very minimal. In this event, and if no other cause of infertility is found, then a diagnosis of unexplained infertility may be warranted.

The diagnosis can be made in a number of ways. Your doctor may suggest a laparoscopy and hydrotubation. A camera is placed through your belly button (usually) to inspect the pelvis. This is especially useful if other features are present e.g. pain which might suggest endometriosis (often treated at the same time). Dye is passed through the tubes and patency (or blockage or swelling) confirmed. The most common cause of blocked tubes is infection (PID) of which the most common infection is chlamydia. About 70% of women who have blocked tubes have had a chlamydia infection although it is often silent and they will not have even been aware of it.

A less invasive test still carried out in some hospitals is called a hysterosalpingogram. It is a useful test but is being superseded in many parts of the world by HyCoSy or saline sonography. These do not require X-Ray technology but rather vaginal ultrasound (like you may have when being monitored for fertility treatment). HyCoSy uses a special contrast dye while the saline test uses sterile salty water (saline). These are much less invasive than the older tests and may themselves be overtaken by three-dimensional ultrasound in years to come.

Endometriosis

Endometriosis arises when tissue, which normally lines the womb, is found at other sites in the pelvis. Some women with Endometriosis are without symptoms, but others suffer with painful periods and pain during intercourse. Endometriosis can appear as spots or patches called implants or as cysts on the ovaries and in severe cases can affect surrounding tissue causing adhesions or scar tissue. The diagnosis of Endometriosis cannot be made from symptoms alone as some women have no symptoms as there may be other reasons for pelvic pain.

Laparoscopy is the most effective way to diagnose the condition by directly visualising the pelvis and may be required before embarking upon an IVF cycle. It is carried out by inserting a small telescope through an incision close to the naval.

During a laparoscopy, the surgeon can also clarify if the tubes are open. This is where liquid is flushed through the neck of the womb. This flushing with liquid is similar to Saline Infusion Hysterosonography which is carried out on all female patients pre-IVF at Sims.

Many women who have Endometriosis can conceive without any difficulty however some women do have difficulty getting pregnant. IVF is an appropriate treatment for infertility associated with endometriosis where other methods have failed.

PCOS

What is PCOS?

Polycystic ovary syndrome is a complete misnomer for a common condition affecting women, classically during their fertile years. First of all there are no “cysts” per se, just small follicles in the ovary which get stuck at a certain stage of development before they can get to the stage of producing an egg (at about 6-8 mm). This is the reason these patients are often infertile – i.e. because they are not producing eggs.

Why does this happen?

In fact the reason these women have this condition appears ultimately related to evolutionary pressures on human populations related to food (or more particularly the absence of food). Women with PCO are insulin resistant and therefore store energy very efficiently i.e. “super savers”. This is all well and good in time of famine when the food supply is poor. In these circumstances, they will utilise these body stores (body fat), their body mass is reduced (they slim down), they consequently become more sensitive to insulin, and then begin to ovulate (produce an egg). In summary then they appear to be designed for times of famine (a common situation during human existence on planet earth).

I understand PCOS is very common. Why is that?

In contrast, in early twenty-first century Ireland (as in other developed countries), you can hardly step out your door without being assaulted with highly processed foods (especially carbohydrates) of all sorts – biscuits, breakfast cereal, cakes, crisps, tortilla chips, pizza, white bread, pasta, etc. Intake of these “high glycaemic” foods (i.e. high sugar) immediately elevates the insulin level and most of what has been consumed is stored for the future (the body is still waiting for famine, remember?). This surge of insulin then drops the blood sugar and the unwilling victim (maybe you) is starving again only an hour or two having eaten – and looking for another “hit” (e.g. that enticing maple pecan pastry with the mid-morning coffee). Thus the body lurches from sugar high to sugar low, storing for posterity along the way.

What problems do this cause?

The problem with this is not just the expanding waistline, but further induced resistance to insulin and the condition therefore gets worse over time. A downward spiral into metabolic no-woman’s land. One serious long term health consequence associated with this worsening insulin resistance and associated truncal obesity (i.e. expanding waistline) is the increased risk of metabolic syndrome arising from this. The features of this condition are high cholesterol, high blood pressure, diabetes in later life, and ultimately heart disease. In fact, men also have these although it has no similar effect on their fertility (i.e. polycystic testicles). Thus a tendency to PCOS caused by insulin resistance can be inherited on the male side although the full genetic picture has yet to be made clear.

How does PCOS reveal itself?

The classic complaints of the PCOS woman are irregular periods or no periods, often heavy and prolonged when they do come (due to a build up of the thickness of the lining of the womb over months or years without a period). She may be prone to being overweight (although not necessarily so), often craves mid-meal snacks (remember the sugar hits?), is often tired and may also complain of pelvic pain (in the lower part of the tummy). The reason for the lower tummy pain is that the uncontrolled insulin resistance is associated with an elevation of LH from the pituitary gland. This in turn stimulates the theca cells in the centre (“stroma” or substance) of the ovary to produce lots of male hormone. These cells enlarge and stretch the cortex (outside skin) of the ovary causing the ill defined pain. Clearly the condition must be metabolically out of control for the cortex to stretch and pain is therefore not a particularly good sign.

You mentioned male hormones. Why do women have male hormones?

Male hormones (also called androgens e.g. androstenedione or dihydroepiandrosterone) are produced by both women and men – it is just the proportion and absolute amounts of each which vary. In fact is essential for the ovary (i.e. theca cells) to produce male hormones which are then converted by other cells in the ovary (called granulosa cells) to female hormones. This female hormone is called oestradiol and is essential for ‘oestrus’ i.e. egg production. So the humble male hormone has some use after all – even in women!

What else might you experience (if you had PCOS)?

If we think of the chain reaction from insulin to the pituitary gland and the ovary (as discussed above), then must the excess male hormone also have an effect? Yes, it does. As the polycystic ovary becomes a factory for industrial levels of male hormone production, so the unwanted effects of these androgens (“androgenic effects”) become apparent. This is mostly acne on the face and / or unwanted facial hair (hirsuitism) on the upper lip, chin, around the nipples or on the tummy.

Thus you can see that the original description of PCOS comes about, i.e. amenorrhoea (no periods, hirsuitism (too many male hormones), and enlarged polycystic ovaries (follicles stuck in mid development, swollen centre of ovary from theca cells producing male hormone).

Treatment for PCOS

Can any thing be done? Yes it can.. The first place to look at is the underlying cause(s) so anything that increases insulin sensitivity is worthwhile. The most obvious of these is exercise (about half an hour a day) followed by using a “low glycaemic index diet”.

What is a low glycaemic index diet?

If you remember the problem of high sugar releasing foods above, then the answer is to eat foods which release small amounts of glucose and therefore reduce the corresponding surges of insulin. These then level out the glucose / insulin levels allowing your body to use the food energy consumed for daily activity rather that storing most of it for future use around the liver or in fat. These foods include oats, porridge, bran or wholemeal bread, beans, peas, plums, apples, etc. Lean meats are also good because they do not cause a surge in insulin. The striking thing about many of these is how “natural” they are – the long and the short of it is that many (if not most) of us are poorly designed to cope with the highly processed foods that surround us - and this explains to a large extent (along with sedentary lifestyles), the epidemic of obesity evident in Western countries.

Medicine to increase insulin sensitivity

The next step is medications to increase sensitivity to insulin, the most widely used of which is Metformin. Now many health professionals are themselves unaware of the benefits of these agents in PCOS (apart from their conventional use in diabetics). However they have been clearly shown to improve outcomes in infertile patients with PCOS including ovulation (egg production) and pregnancy rates after many different types of fertility treatment.

Using the ‘pill’ to suppress the ovary

From the point of view of the ovary, one option is to “turn off” the ovary using the oral contraceptive pill. The trade-name of the particular pill that is commonly used is “Dianette”. It has an additional effect in PCOS because it has “anti-androgenic” properties. This means it acts to reduce the effect of the male hormones that are in the circulation – in addition to suppressing the activity of the ovary. Of course this is only an option if you do not wish to have a family. Other agents can be used to counteract the effect of androgens include steroids (like dexamethasone) or spironolactone.

Surgery to help ovulation

If you do want a family, then it is important to kick start ovulation (i.e. egg production). Stein and Leventhal (see before) suggested taking a chunk out of the ovary. This operation is called a “wedge resection” and was carried out successfully for many decades. In recent years there has been a shift to a less damaging operation which achieves a similar effect – laparoscopic polycystic ovarian drill. Here a telescope is put into the tummy and a needle inserted into the ovary to disrupt it and trigger ovulation. For the purposes of simplicity, you might like to think of it as puncturing the multiple cysts although there is more to it than that.

Fertility treatment

Patients with infertility due to PCOS are often treated successfully, although there are a number of potential problems. The first is that it can be difficult to make them ovulate without getting an over-response. In other words they tend to either under-respond, or over-respond, or both! Under-response tends to occur when aiming for just one follicle to develop in conjunction with either timed sexual intercourse or intrauterine insemination.

The classic case here is of a patient with PCO is “clomid resistant”, i.e. does not respond to a conventional oral drug to stimulate egg production called clomiphene citrate (or “clomid” by its trade-name). Stimulation is then further increased by adding in injections, although bearing in mind the increased possibility of over-stimulation. In fact the patient can develop anything from 4-24 follicles (or more) if she does over-respond. This “hyperstimulation”, if it occurs, needs to be managed carefully and is dealt with elsewhere on this website. If a patient does not respond appropriately to these agents, then IVF is the next step. In this event be reassured that, by and large, patients with PCO are generally successful.

What about my general health?

If, finally, we turn to the effect of these metabolic changes over a lifetime – independent of the issues discussed above – the main ones concern not just the “metabolic syndrome” discussed before but also (a) an increase in the long term risk of cancer of the lining of the womb (carcinoma of the endometrium) and (b) quality of life issues including excessive menstrual bleeding (dysfunctional uterine bleeding). These are best discussed with your doctor. However I think it is a good idea to do some homework before you do so. Bulletin boards on the internet are a good source of information as are specialist support networks for PCOS both in Ireland and overseas. Just google “PCOS” and find out for yourself.

Some reassurance

Although PCOS is a complex condition and can be difficult to manage, it is not insurmountable. The first step is the most difficult to take and it generally gets easier as you go along. Baby steps include the exercise and diet changes, and these may be all you need. However, even if you need other medical, surgical, or fertility treatment they are a good basis on which to get started. Good Luck from all of us here at Sims.