INFERTILITY-OVERVIEW

What is Infertility?

In the simplest of terms, Infertility may be described as the inability to conceive despite conscious attempts.

However, as gynaecologists, we are more specific while defining Infertility. It is the inability to conceive even after two year of unprotected intercourse.

It is estimated that about 84% of couple conceive spontaneously within one year of unprotected intercourse while another 7% conceive over the next 12 months, such that the cumulative pregnancy rate is about 92% at the end of 24 months. Hence, it is justified to investigate apparently healthy, young couple after 2 years of inability to conceive.

 However, the time frame of two years is made less stringent if the couple are elderly (the woman more than 35 years) or either of them has a pre-existing problem. Example- the woman having polycystic ovaries or endometriosis or her partner having abnormalities of the semenal parameters.

What is not infertility?

Young, healthy couple who have not been able to conceive within 12 to 18 months of staying together.

Couple who are using contraceptives to avoid pregnancy, obviously!

Couple who have difficulty in their sexual performance. Example-Problems of erection or ejaculation in men and sexual aversion disorders in women.

Couple who are beyond the reproductive age.

Why is it important to define if a couple is or not infertile?

Without a set definition, we may unnecessarily be investigating many normal couple and of course, get credited for helping them achieve pregnancy... when in reality, they would have conceived anyway over the next few months!

However, branding a couple as infertile puts them under a great deal of mental tension. We all know that the hormones secreted in the brain play an important role in maintaining normal sexual cycles and hence stress may interfere with the normal functioning of the brain and secretion of hormones. The classical example quoted is that of many childless couple who, after years of trying, finally give up and adopt a child. As the stress of trying to conceive is lifted, many of them find that the woman has conceived spontaneously over the next few months!

With the advent of modern Medicine and methods, the treatment of infertility has become varied, complex and very individualistic. Treatment is often exacting in terms of money, time and interventions. Hence, it is always with great caution and consideration that a couple must be labeled as infertile.

The patient load on Medical personnel is also greatly reduced with proper definition and classification of Infertility.

Finally, despite all the modernization, Infertility often carries a social stigma, which is very traumatic, especially to the woman, affecting her mental well-being and curtailing her social activities.

Types of Infertility

Primary infertility is when the couple has been unable to conceive at all.

Secondary infertility is when the couple, irrespective of the outcome of pregnancy, has achieved pregnancy at least once. Example: Couple not able to have another child after years of their first or couple who have had at least one miscarriage is secondarily infertile.

Infertility can be also categorized as due to male factor or female factors or combined factors and finally, as unexplained Infertility (when no apparent cause can be detected in either partner)

Further, female infertility can be classified as due to Ovarian Cause (problems of inappropriate ovulation-production of eggs by ovary), Tubal cause (blockage or other diseases of the uterine tubes), Uterine causes, Hormonal causes and finally as due to Endometriosis (multiple cause)

Male factor infertility can be due to Semenal abnormalities (Complete absence of sperms-Azoospermia, reduction in sperm numbers-Oligospermia, insufficient motility of sperms-asthenospermia, abnormal physical characterisitics-teratospermia or a combination of these), Drugs(including tobacco, alcohol and cancer therapy), defective genes(as in Klinefelter’s syndrome or Cystic Fibrosis), Past infections of the testes(Mumps, tuberculosis), Auto immune conditions, exposure to irradiation or chemicals ;or certain medical disorders etc.

Combined factor infertility is when both partners have problems pertaining to fertility.

Unexplained Infertility or Idiopathic infertility is when all the tests in both the partners are apparently normal. Needless to say, with advancing investigative technologies the percentage in this category is expected to diminish.

Can infertility be classified as curable or correctable?

This is obviously an Ethical question. If the solution for infertility is having a child, then this can be most easily corrected by adopting a child! Only when pregnancy has been achieved after correcting the underlying medical condition, can infertility be technically termed to be ‘cured’!

Other Ethical and Social aspects in Infertility:

In India, it is very common for childless couple to resort to various religious practices in the hope of propitiating the Unknown to bless them with children.

Also, a vast majority of people believe childlessness is because of a defect in the woman only. The basic knowledge that it takes a man and a woman to make children is completely lost on them! Even educated families believe so and infertility is a very easily accepted reason-by both parties and families- for the man to re-marry! I know many women who are normal but have remained childless because their husbands refuse to be examined, or even have one Semen analysis done (Which if carried out at all, always shows that it is defective). Men have re-married hoping the second wife will conceive only to find out years later that they had no sperms in their semen!

Management and treatment of Infertility in the Allopathic field of Medicine scales new heights every hour! The IVF-ET (Test-tube babies) is so commonplace these days and scientists are looking at Designer babies now. Yet, even educated people resort to dangerous practices, believing it to be alternative medicine.

Ethically, many issues concerned with artificial reproduction (Like Donor insemination, surrogacy, egg/embryo donation) have not been addressed at all. This could lead to serious problems in later life for all the parties concerned.

In India, there is no authentic body responsible for the regulation and monitoring of the treatment of infertility and this has led to the abuse of advanced technologies by both patients and the treating doctors.

CONCLUSION:

It is therefore very important to recognize infertility, categorize it as best as possible and counsel the couple on all the possible ‘treatments’ and ‘cures’ available. Finally, treatment must be tailored to the needs of individual patient.

The patients, doctors and the families must acknowledge that management and treatment of infertility is unlike that of any other disease. Because the result impacts the lifetime of two generations, the society and the profession of the treating doctor.

Polycystic ovarian Syndrome (PCOS)

Polycystic Ovaries on Ultrasound

1. What is a polycystic ovary?

A polycystic ovary (Poly-multiple, cyst-fluid filled structure) is characterized by the presence of numerous, small (8-10mm sized) fluid filled structures all over its surface. This is in contrast to a normal ovary which may have none or 1-3 developing follicles in one menstrual cycle.

 Actually these fluid filled structures are immature eggs surrounded by fluid and are called follicles.

Polycystic Ovarian Syndrome is also known as Stein-Levinthal Syndrome (named after its discoverers)

Model of Polycystic ovaries

2. What is the cause of Polycystic Ovarian Syndrome? 

The final defect in PCOS is hormonal impairment. However the cause is now regarded as multifactorial. Insulin resistance, low grade inflammation and even an impairment of genetic expression in foetal life have been attributed to cause PCOS. Genetic factors (Higher incidence amongst siblings or mother-daughter-granddaughter), environmental factors (excessive weight), metabolic derangement (obesity and impaired glucose metabolism) are all postulated to contribute to the condition.

3. Why is PCOS important?

Ovaries are the reproductive organs responsible for producing eggs and the female hormones. Hence they are important for natural conception and regularity of menstrual cycle. In PCOS there is impairment of ovarian functions.

Thus it follows that in PCOS there is impaired production of eggs and hence associated menstrual and hormonal irregularities .This naturally affects not only the menstrual cycle of a woman but also her fertility.

PCOS is also associated with other medical conditions and long term effects as enumerated below.  

4. What is the incidence of PCOS in India?

PCOS is the most common hormonal reproductive problem in women of childbearing age. The incidence is believed to be on a rise in India. A modest estimate is that 7-10% of women in the reproductive age group (15-45 years) suffer from this condition. But in pracgice the incidence is noted to be much higher.

5. What are the features of PCOS?

Women may have varied features. These include:

a)      Irregularity in menstruation: Delayed cycles and/or scanty flow. Absent menstruation for several months or menstruation occurring only after hormonal therapy. Some women may have continuous flow following periods of absent menstruation.

b)      Excessive weight-Most PCOS patients are overweight or obese. However PCOS can occur in underweight women also.

c)      Facial hair, acne (pimples) and loss of hair from the temple region. These features are medically termed as hyperandrogenic features and are attributed to excess circulating male hormones. Acanthosis Nigricans is black discoloration of the nape of neck, axillae and under the breasts and is often indicative of insulin resistance.

d)     Inability to conceive: This results due to improper or absent production of eggs from the ovaries.

e)      Other hormonal impairments: PCOS patients often have impaired glucose metabolism which causes increased blood sugars. Levels of Prolactin (hormone secreted by the pituitary gland in the brain) may also be raised. LH (Luteinizing hormone, also secreted by pituitary) which is responsible for production of eggs is classically raised 3 times over its sister hormone FSH (Follicular Stimulating Hormone)-though this is no longer a required criterion for diagnosis.

f)       Ultrasound diagnosis: On ultrasound scan, the ovaries are classically enlarged with raised volumes and each shows over 10-12 clear follicles of 8-10mms. This is one of the latest internationally accepted criteria for diagnosis of PCOS. The other two are menstrual irregularities and features of androgenization (see c)

6. What are the long term consequences of PCOs?
      Patients with PCOS have inability to conceive. This is due to absent/unhealthy egg production and also because of the multitude hormonal derangements that occur in this condition.
      It is now established that patients with PCOS are prone to develop diabetes (non-insulin dependent or Type II diabetes), impaired lipid metabolism (Dyslipidemia) and ischaemic heart disease (reduce blood supply to heart causing heart attacks).The associated obesity is also a contributory risk factor to these conditions.
      Prolonged periods of absent menstruation and hence impaired levels of the female hormone, estrogen,           makes these women prone for osteoporosis (loss of calcium from bones) and its attended     complications.

PCOS patients are at an increased risk of developing cancers of the breast, endometrium (lining of

uterus) and maybe ovary at a later stage in life.
PCOS patients who conceive are believed to be at a higher risk for mis-carriages and pregnancy induced hypertension during their pregnancy.

Also the psychological impact of impaired menstruation, infertility, obesity, facial hair and acne cannot be under estimated though not completely quantified.

7. Can PCOS be treated?

      Yes, but not to complete satisfaction at times. It is very disappointing many a times because the patient, who got better with treatment, reverts back to impaired functioning a few months after medications have been stopped.

8. What are the modalities of treatment for PCOS?

a) Lifestyle modification:

 As obesity is one of the features and a contributory factor to PCOS, it helps greatly if patients strive to reduce weight. Even a modest weight reduction of 4-5 kgs works wonders as patients begin to respond better to treatment. It is advisable to maintain your BMI (Body Mass Index, which is calculated based on height and weight of an individual) between 20 and 25. 

b) Medical treatment:

Treatment of PCOS needs to be tailored to suit each patient. It depends upon the main complaint of the patient and her requirements. For a 20 year old, the problem could be of acne and irregular periods; and for a married woman it could be inability to conceive and for many others their irregular cycles or facial hair may be disconcerting.

Options available are

• Oral contraceptive pills: A wide variety of combinations are available to suit the needs of every patient depending on her symptoms. Oral Pills regularize the cycles, correct the underlying hormonal problems to some extent and offer contraception to those not wanting to conceive. For women desiring to conceive, oral pills are offered for a few months before starting treatment.
•  Drugs for treatment of infertility: Clomiphene citrate is a drug which induces the formation of eggs from the ovary. It may be used alone or in combination with hormonal injections like the hCG (Human Chorionic Gonadotropins) or hMG (Human Menopausal Gonadotropins) or FSH (Follicle Stimulating Hormone) or GnRH (Gonadotropin Releasing Hormone analogues) These medications are used to aid the formation and release of eggs and hence help achieve pregnancy.
•  Metformin: This is often used in the treatment of mild diabetes. Since PCO is associated with impaired glucose metabolism, metformin helps to correct the underlying impairment. Dosage for PCOs: 1500mgs/day in divided doses.
•  Co-therapies: Medications to reduce weight (orlistat) are used in obese patients, medications and mechanical methods (laser, electrolysis, waxing) are employed for patients with facial hair. Oral pills which contain Cyproterone Acetate help in clearing the face of acne while those with Drosperinone may reduce rate of facial hair growth.

c) Surgical treatment: The multiple cysts present on the ovaries are punctured to let out the ‘unhealthy’ follicular fluid by a key-hole surgical procedure called Laparoscopic Ovarian Drilling (LOD). Around 4-6 punctures are made in each ovary. This procedure improves the internal environment of the ovaries and also makes them more responsive to drugs during the future course of treatment.

LOD (Laparoscopic Ovarian drilling)

9) What is PCOS in a nutshell?

•   PCOS is quite a common condition with a wide variety of manifestations.
•  The exact cause of PCOS is still not yet established. It could be familial.
•  PCOS needs to be treated as they have current and long term consequences for a woman.
•  The treatment of PCOS is to be tailored to an individual and may span several months.
•  Any ovary with cysts is NOT a PCOS. It has set criteria to be satisfied and you need to consult the specialist.

THE NORMAL MENSTRUAL CYCLE

Menstruation is a part of the female reproductive cycle that begins when a girl becomes sexually mature at puberty. It is the periodic discharge of blood and tissues from the uterus. Cyclical changes occurring from one menstruation to the next constitute a menstrual cycle. Until menopause, menstruation occurs approximately every 28 ± 4 days (excluding the period when a woman is pregnant.)

The importance of menstrual cycle:

During the menstrual cycle, an egg is released from the ovary even as the womb (uterus) prepares itself for housing and protecting the resulting embryo, if this egg were to be fertilized by a sperm. If however, the egg is not fertilized, the lining of the womb (which was prepared in anticipation) is shed from the body as periods. The menstrual blood flows out from the uterus through its mouth (the cervix) and out of the body through the vagina.

The menstrual cycle is unique because it limits the fertility of a woman to the specific period of ovulation. (Production of egg) This is in contrast to a man’s physiology where significant numbers of sperms are produced during every ejaculation. The menstrual cycle is associated with not only changes in the reproductive organs but also changes in the breast, body fluids, the basal body temperature and other organs.

Girls begin their first period around 12 years and this is called Menarche. Menarche occurs approximately 2 years after they begin to develop breasts (thelarche). During this interval, girls experience sudden growth spurt and other bodily changes. Menarche for some girls may be as early as at eight or as late as at 16 years. There may occur an increased amount of clear vaginal discharge a few months before their first period.

The cessation of menstruation is called menopause and occurs around 50 years of age.

OVERVIEW OF THE MENSTRUAL CYCLE   

WHAT IS A NORMAL CYCLE?

For the ease of understanding, the normal menstrual cycle may be studied as the Menstrual Phase, Follicular (Proliferative) phase, Ovulation and the Luteal (Secretory) Phase.

1. MENSTRUAL PHASE

Tough the typical cycle length is about 28 days; it may vary between 26 to 33 days without significant alteration in function. The flow usually lasts for 3-5 days. The estimated blood loss per cycle is between 30 to 50 milliliters.

During menstruation, the lining of the uterus (endometrium) shrinks as it is being partially shed due to withdrawal of hormones and hence insufficient blood supply.

2. FOLLICULAR PHASE (PROLIFERATIVE PHASE):

This is the period of menstrual cycle before ovulation. It is the duration after cessation of menses and up to the 13^th day of a 28-day cycle. (Approximately 10 days)It is mainly under the influence of the Follicular Stimulating Hormone (FSH) secreted in the Pituitary Gland.

It is called Follicular Phase because the follicles (tissues that house single eggs) begin to grow and develop now. It is also called proliferative because of the changes that occur in the lining of the uterus (Endometrium)

Every cycle,a group of 6-10 or more follicles begin to grow during this phase, increasing in size while simultaneously producing the important female hormone, the Estrogen. However, of all the follicles developing, only one is destined to ovulate and the rests undergo atresia. (Cell death)The follicle housing the egg, which is destined to be released in that cycle, is called the dominant follicle.

 The dominant follicle can be imagined as a tiny (about 20-millimeter diameter) fluid filled tissue ball with an internal protrusion, where the precious egg is ensconced. The egg is seated on a mass of nutritious cells, surrounded by nourishing fluid! 

Estrogen is the main hormone of the Follicular Phase and has profound effect on the endometrium. The endometrium, which was all shed off, but for its basal layer, (during menstruation), now begins to regrow under the influence of estrogen. The blood vessels, glands and tissues of the endometrium are all influenced to grow and change favorably in preparation for a fertilized egg!

Ovulation occurs at the end of the Follicular Phase.

3. OVULATION (Release of egg from the ovary)

Ovulation occurs 14 days BEFORE the next cycle is due. For example:  on the 14^thday of a 28-day cycle or on the 16^th day of a 30-day cycle or 12^th day of a 26-day cycle. It occurs within hours after a sudden surge in the release another Pituitary gland hormone, the Luteinizing Hormone (LH).

The egg, which is released from the ovary, is picked up by the uterine tube. It stays within the tube for about 24 hours and is actually anticipating to be fertilized by a sperm! If fertilization does not occur during this time, the egg self-destructs! (This interesting phenomenon of programmed cell death or apoptosis, is also known as cellular suicide!) 

OVULATION    

4. LUTEAL PHASE (SECRETORY PHASE):  

Immediately after Ovulation is the Luteal or Secretory Phase of the menstrual cycle. Irrespective of the initial cycle length, an ideal Luteal Phase is ALWAYS 14 days.

It is called Luteal Phase because of the Corpus luteum (see below) and Secretory Phase because of an increase in the endometrial glandular secretions.

  With the release of the egg, the dominant follicle is now a collapsed mass of cells called the corpus luteum (Yellow body-because it looks yellow due to high lipid content). The corpus luteum begins to secrete estrogens and importantly large quantities of progesterone-which is the chief hormone of the Luteal Phase. Progesterone also acts on the uterus, continuing to modify it favorably for receiving the fertilized egg.

When the egg is fertilized, the corpus luteum (Called Corpus Luteum of Pregnancy) becomes more active and is in fact responsible for sustaining the growing Embryo up to 10-12 weeks of early intrauterine life.

If however there is no fertilization, the corpus luteum self-destructs by about the 21^st -22^nd day and sets off a cascade effect. As further production of estrogen and progesterone cease, their sustained effect on the endometrium is hampered. This disrupts the growth of the glands, tissues and blood vessels and hence the superficial layer of the endometrium, begins to peel off from the basal layer. These are shed as menses on the 28^th day, thus completing the cycle; before the next one begins.   

CHANGES OCUURING IN THE ENDOMETRIUM (LINING OF UTERUS)