INFERTILITY AND IT'S CAUSES

Infertility refers to an inability to conceive after having regular unprotected sex. Infertility can also refer to the biological inability of an individual to contribute to conception, or to a female who cannot carry a pregnancy to full term. In many countries infertility refers to a couple that has failed to conceive after 12 months of regular sexual intercourse without the use of contraception.

Studies indicate that slightly over half of all cases of infertility are a result of female conditions, while the rest are caused by either sperm disorders or unidentified factors. According to The Mayo Clinic, USA:

• About 20% of cases of infertility are due to a problem in the man.
• About 40% to 50% of cases of infertility are due to a problem in the woman.
• About 30% to 40% of cases of infertility are due to problems in both the man and the woman.

According to Medilexicon's medical dictionary, infertility is "Diminished or absent ability to produce offspring; in either the male or the female, not as irreversible as sterility."

According to the Department of Health and Human Services, USA, approximately 10% to 15% of couples in the USA are infertile - meaning they have not conceived after at least one year of regular, unprotected sex.

Many cases of apparent infertility are treatable. Infertility may have a single cause in one of the partners, or it could be the result of a combination of factors.

Chances of conceiving within one year

In Europe, North America and much of the world approximately 85% of couples will conceive within one year if they have regular unprotected sex. Averages in the UK are as follows (National Health Service):

• 20% will conceive within one month
• 70% will conceive within six months
  
• 85% will conceive within 12 months
• 90% will conceive within 18 months
• 95% will conceive within 24 months

Therefore, doctors in the UK will not usually diagnose a couple as infertile until 24 months have passed without conception and regular unprotected sex. Most people will see their GP (general practitioner, primary care physician) if there is no pregnancy within 12 months.

According to the National Health Service, UK, a couple that has been trying to conceive for over three years has a maximum 25% chance of conceiving over the subsequent 12 months if they continue trying.

What are the risk factors of infertility?

In medicine, a risk factor is something that raises the risk of developing a condition, disease or symptom. For example, obese people are more likely to develop diabetes type 2 compared to people of normal weight; therefore, obesity is a risk factor for diabetes type 2.

• Age - a woman's fertility starts to drop after she is about 32 years old, and continues doing so. A 50-year-old man is usually less fertile than a man in his 20s (male fertility progressively drops after the age of 40).


• Smoking - smoking significantly increases the risk of infertility in both men and women. Smoking may also undermine the effects of fertility treatment. Even when a woman gets pregnant, if she smokes she has a greater risk of miscarriage.


• Alcohol consumption - a woman's pregnancy can be seriously affected by any amount of alcohol consumption. Alcohol abuse may lower male fertility. Moderate alcohol consumption has not been shown to lower fertility in most men, but is thought to lower fertility in men who already have a low sperm count.


• Being obese or overweight - in industrialized countries overweight/obesity and a sedentary lifestyle are often found to be the principal causes of female infertility. An overweight man has a higher risk of having abnormal sperm.


• Eating disorders - women who become seriously underweight as a result of an eating disorder may have fertility problems.


• Being vegan - if you are a strict vegan you must make sure your intake of iron, folic acid, zinc and vitamin B-12 are adequate, otherwise your fertility may become affected.


• Over-exercising - a woman who exercises for more than seven hours each week may have ovulation problems.


• Not exercising - leading a sedentary lifestyle is sometimes linked to lower fertility in both men and women.


• Sexually transmitted infections (STIs) - chlamydia can damage the fallopian tubes, as well as making the man's scrotum become inflamed. Some other STIs may also cause infertility.


• Exposure to some chemicals - some pesticides, herbicides, metals (lead) and solvents have been linked to fertility problems in both men and women.


• Mental stress - studies indicate that female ovulation and sperm production may be affected by mental stress. If at least one partner is stressed it is possible that the frequency of sexual intercourse is less, resulting in a lower chance of conception.

Causes of infertility in women

• Ovulation disorders - problems with ovulation are the most common cause of infertility in women, experts say. Ovulation is the monthly release of an egg. In some cases the woman never releases eggs, while in others the woman does not release eggs during come cycles. Ovulation disorders can be due to:
  
  
  • Premature ovarian failure - the woman's ovaries stop working before she is 40.
  
  
  • PCOS (polycystic ovary syndrome) - the woman's ovaries function abnormally. She also has abnormally high levels of androgen. About 5% to 10% of women of reproductive age are affected to some degree. Also called Stein-Leventhal syndrome.
  
  
  • Hyperprolactinemia - if prolactin levels are high and the woman is not pregnant or breastfeeding, it may affect ovulation and fertility.
  
  
  • Poor egg quality - eggs that are damaged or develop genetic abnormalities cannot sustain a pregnancy. The older a woman is the higher the risk.
  
  
  • Overactive thyroid gland
  
  
  • Underactive thyroid gland
  
  
  • Some chronic conditions, such as AIDS or cancer.


• Scientists discover gene that explains infertility - scientists from the University of Edinburgh reported in the Journal of Cell Science that they identified a gene that controls a vital process in the formation of healthy fertile eggs.
  
  They say their breakthrough will help researchers better understand how cells divide during reproduction, which in turn will help explain low fertility and sterility.
  
  This gene allows chromosomes to bunch up together. The authors believe that this huddling of chromosomes secures the healthy development and subsequent fertilization of an egg.
  
  They analyzed hundreds of infertile Drosophila oocytes (fruit flies) and found that without the gene SRPK, the chromosomes do not huddle together. This gene exists in human cells.
  
  The researchers said that "the absence of SRPK ultimately leads to sterility and low fertility".


• Problems in the uterus or fallopian tubes
  
  The egg travels from the ovary to the uterus (womb) where the fertilized egg grows. If there is something wrong in the uterus or the fallopian tubes the woman may not be able to conceive naturally. This may be due to:
  
  
  • Surgery - pelvic surgery can sometimes cause scarring or damage to the fallopian tubes. Cervical surgery can sometimes cause scarring or shortening of the cervix. The cervix is the neck of the uterus.
  
  
  • Submucosal fibroids - benign or non-cancerous tumors found in the muscular wall of the uterus, occurring in 30% to 40% of women of childbearing age. They may interfere with implantation. They can also block the fallopian tube, preventing sperm from fertilizing the egg. Large submucosal uterine fibroids may make the uterus' cavity bigger, increasing the distance the sperm has to travel.
  
  
  • Endometriosis - cells that are normally found within the lining of the uterus start growing elsewhere in the body.
  
  
  • Previous sterilization treatment - if a woman chose to have her fallopian tubes blocked. It is possible to reverse this process, but the chances of becoming fertile again are not high. However, an eight-year study showed tubal reversal surgery results in higher pregnancy and live birth rates and is less costly than IVF.


• Medications - some drugs can affect the fertility of a woman. These include:
  
  
  • NSAIDs (non-steroidal anti-inflammatory drugs) - women who take aspirin or ibuprofen long-term may find it harder to conceive.
  
  
  • Chemotherapy - some medications used in chemotherapy can result in ovarian failure. In some cases, this side effect of chemotherapy may be permanent.


• Radiotherapy - if radiation therapy was aimed near the womans reproductive organs there is a higher risk of fertility problems.


• Illegal drugs - some women who take marijuana or cocaine may have fertility problems.

Causes of infertility in men

Semen

Semen is the milky fluid that a man's penis releases during orgasm. Semen consists of fluid and sperm. The fluid comes from the prostate gland, seminal vesicle and other sex glands. The sperm is produced in the testicles. During orgasm a man ejaculates (releases semen through the penis). The seminal fluid helps transport the sperm during ejaculation. The seminal fluid has sugar in it - sugar is an energy source for sperm.

Abnormal semen is responsible for about 75% of all cases of male infertility. Unfortunately, in many cases doctors never find out why. The following semen problems are possible:

• Low sperm count (low concentration) - the man ejaculates a lower number of sperm, compared to other men. Sperm concentration should be 20 million sperm per milliliter of semen. If the count is under 10 million there is a low sperm concentration (subfertility).


• No sperm - when the man ejaculates there is no sperm in the semen.


• Low sperm mobility (motility) - the sperm cannot "swim" as well as it should.


• Abnormal sperm - perhaps the sperm has an unusual shape, making it more difficult to move and fertilize an egg.

Sperm must be the right shape and able to travel rapidly and accurately towards the egg. If the sperm's morphology (structure) and motility (movement) are wrong it is less likely to be able to reach the egg and fertilize it.

The following may cause semen to be abnormal:

• Testicular infection


• Testicular cancer


• Testicular surgery


• Overheating the testicles - frequent saunas, hot tubs, very hot baths, or working in extremely hot environments can raise the temperature of the testicles. Tight clothing may have the same effect on some people.


• Ejaculation disorders - for some men it may be difficult to ejaculate properly. Men with retrograde ejaculation ejaculate semen into the bladder. If the ejaculatory ducts are blocked or obstructed the man may have a problem ejaculating appropriately.


• Varicocele - this is a varicose vein in the scrotum that may cause the sperm to overheat.


• Undescended testicle - one (or both) testicle fails to descend from the abdomen into the scrotum during fetal development. Sperm production is affected because the testicle is not in the scrotum and is at a higher temperature. Healthy sperm need to exist in a slightly lower-than-body temperature. That is why they are in the scrotum, and not inside the body.


• Hypogonadism - testosterone deficiency can result in a disorder of the testicles.


• Genetic abnormality - a man should have an X and Y chromosome. If he has two X chromosomes and one Y chromosome (Klinefelter's syndrome) there will be an abnormal development of the testicles, low testosterone, and a low sperm count (sometimes no sperm at all).


• Mumps - this viral infection usually affects young children. However, if it occurs after puberty inflammation of the testicles may affect sperm production.


• Hypospadias - the urethral opening is at the underside of the penis, instead of its tip. This abnormality is usually surgically corrected when the male is a baby. If it is not the sperm may find it harder to get to the female's cervix. Hypospadias occur in about 1 in every 500 newborn boys.


• Cystic fibrosis - Cystic fibrosis is a chronic disease that affects organs such as the liver, lungs, pancreas, and intestines. It disrupts the body's salt balance, leaving too little salt and water on the outside of cells and causing the thin layer of mucus that usually keeps the lungs free of germs to become thick and sticky. This mucus is difficult to cough out, and it clogs the lungs and airways, leading to infections and damaged lungs. Males with cystic fibrosis commonly have a missing or obstructed vas deferens (tube connecting the testes to the urethra; it carries sperm from the epididymis to the ejaculatory duct and the urethra).


• Radiotherapy - radiation therapy can impair sperm production. The severity usually depends on how near to the testicles the radiation was aimed.


• Some diseases - the following diseases and conditions are sometimes linked to lower fertility in males:
  
  
  Anemia
  Cushing's syndrome
  Diabetes
  Thyroid disease


• Medications
  
  
  Sulfasalazine - this anti-inflammatory drug can significantly lower a man's sperm count. The drug is often prescribed for patients with Crohn's disease or rheumatoid arthritis. Usually this side effect goes away after the patient stops taking the medication.
  
  Anabolic steroids - often taken by bodybuilders and athletes; anabolic steroids, especially after long term use can seriously reduce sperm count and mobility.
  
  Chemotherapy - some medicines may significantly reduce sperm count.


• Illegal drugs - consumption of marijuana and cocaine can lower a man's sperm count.

Diagnosing infertility

Most people will visit their GP (general practitioner, primary care physician) if there is no pregnancy after 12 months of trying. For anybody who is concerned about fertility, especially if they are older (women over 35), it might be a good idea to see a doctor earlier. As fertility testing can sometimes take a long time, and female fertility starts to drop when a woman is in her thirties, seeing the doctor earlier on if you are over 35 makes sense.

A GP can give the patient advice and carry out some preliminary assessments. As it takes two to make a baby it is better for both the male and female to see the doctor together.

Before undergoing testing for fertility it is important that the couple be committed. The doctor will need to know what the patients' sexual habits are, and may make recommendations regarding them. Tests and trials might extend over a long period. Even after thorough testing, no specific cause is ever found for 30% of infertility cases.

In some countries where universal healthcare cover does not exist, evaluation and eventual treatment may be expensive.

Tests for males

• General physical exam - the doctor will ask the man about his medical history, medications, and sexual habits. The physician will also carry out an examination of his genitals. The testicles will be checked for lumps or deformities, while the shape and structure of the penis will be examined for any abnormalities.


• Semen analysis - the doctor may ask for some specimens of semen. They will be analyzed in a laboratory for sperm concentration, motility, color, quality, infections and whether any blood is present. As sperm counts can fluctuate, the man may have to produce more samples.


• Blood test - the lab will test for several things, including the man's level of testosterone and other male hormones.


• Ultrasound test - the doctor will determine whether there is any ejaculatory duct obstruction, retrograde ejaculation, or other abnormality.


• Chlamydia test - if the man is found to have Chlamydia, which can affect fertility, he will be prescribed antibiotics to treat it.

Tests for females

• General physical exam - the doctor will ask the woman about her medical history, medications, menstruation cycle, and sexual habits. She will also undergo a gynecological examination.


• Blood test - several things will be checked, for example, whether hormone levels are correct and whether the woman is ovulating (progesterone test).


• Hysterosalpingography - fluid is injected into the woman's uterus which shows up in X-ray pictures. X-rays are taken to determine whether the fluid travels properly out of the uterus and into the fallopian tubes. If the doctor identifies any problems, such as a blockage, surgery may need to be performed.


• Laparoscopy - a thin, flexible tube with a camera at the end (laparoscope) is inserted into the abdomen and pelvis to look at the fallopian tubes, uterus and ovaries. A small incision is made below the belly button and a needle is inserted into the abdominal cavity; carbon dioxide is injected to create a space for the laparoscope. The doctor will be able to detect endometriosis, scarring, blockages, and some irregularities of the uterus and fallopian tubes.


• Ovarian reserve testing - this is done to find out how effective the eggs are after ovulation.


• Genetic testing - this is to find out whether a genetic abnormality is interfering with the woman's fertility.


• Pelvic ultrasound - high frequency sound waves create an image of an organ in the body, which in this case is the woman's uterus, fallopian tubes, and ovaries.


• Chlamydia test - if the woman is found to have Chlamydia, which can affect fertility, she will be prescribed antibiotics to treat it.


• Thyroid function test - according to the National Health Service (UK) between 1.3% and 5.1% of infertile women have an abnormal thyroid.

Treatment options for infertility?

This will depend on many factors, including the age of the patient(s), how long they have been infertile, personal preferences, and their general state of health. Even if the woman has causes that cannot be corrected, she may still become pregnant.

Frequency of intercourse

The couple may be advised to have sexual intercourse more often. Sex two to three times per week may improve fertility if the frequency was less than this. Some fertility experts warn that too-frequent sex can lower the quality and concentration of sperm. Male sperm can survive inside the female for up to 72 hours, while an egg can be fertilized for up to 24 hours after ovulation.

Fertility treatment for men

• Erectile dysfunction or premature ejaculation - medication and/or behavioral approaches can help men with general sexual problems, resulting in possibly improved fertility.


• Varicocele - if there is a varicose vein in the scrotum, it can be surgically removed.


• Blockage of the ejaculatory duct - sperm can be extracted directly from the testicles and injected into an egg in the laboratory.


• Retrograde ejaculation - sperm can be taken directly from the bladder and injected into an egg in the laboratory.


• Surgery for epididymal blockage - if the epididymis is blocked it can be surgically repaired. The epididymis is a coil-like structure in the testicles which helps store and transport sperm. If the epididymis is blocked sperm may not be ejaculated properly.

Fertility treatment for women

• Ovulation disorders - if the woman has an ovulation disorder she will probably be prescribed fertility drugs which regulate or induce ovulation. These include:
  
  
  • Clomifene (Clomid, Serophene) - this medication helps encourage ovulation in females who do not ovulate regularly, or who do not ovulate at all, because of polycystic ovary syndrome (PCOS) or some other disorder. It makes the pituitary gland release more FSH (follicle-stimulating hormone) and LH (luteinizing hormone).
  
  
  • Metformin (Glucophage) - women who have not responded to Clomifene may have to take this medication. It is especially effective for women with PCOS, especially when linked to insulin resistance.
  
  
  • Human menopausal gonadotropin, or hMG, (Repronex) - this medication contains both FSH and LH. It is an injection and is used for patients who don't ovulate on their own because of a fault in their pituitary gland.
  
  
  • Follicle-stimulating hormone (Gonal-F, Bravelle) - this is a hormone produced by the pituitary gland that controls estrogen production by the ovaries. It stimulates the ovaries to mature egg follicles.
  
  
  • Human chorionic gonadotropin (Ovidrel, Pregnyl) - this medication is used together with clomiphene, hMG and FSH. It stimulates the follicle to ovulate.
  
  
  • Gn-RH (gonadotropin-releasing hormone) analogs - for women who ovulate prematurely, before the lead follicle is mature enough during hmG treatment. This medication delivers a constant supply of Gn-RH to the pituitary gland, which alters the production of hormone, allowing the doctor to induce follicle growth with FSH.
  
  
  • Bromocriptine (Parlodel) - this drug inhibits prolactin production. Prolactin stimulates milk production in breast feeding mothers. If non-pregnant, non-breast feeding women have high levels of prolactin they may have irregular ovulation cycles and have fertility problems.

Risk of multiple pregnancies

Injectable fertility drugs can sometimes be the victims of their own success and cause multiple births - when the woman gets pregnant she has twins, triplets, or perhaps more babies in one go. Oral fertility drugs also raise the risk of multiple pregnancies, but much less so than injectable ones. It is important to monitor the patient carefully during treatment and pregnancy. The more babies the mother carries inside her the higher is her risk of premature labor.

If a woman needs an HCG injection to activate ovulation and ultrasound scans show that too many follicles have developed, it is possible to withhold the HCG injection. Couples may decide to go ahead regardless if the desire to become pregnant is very strong.

Multifetal pregnancy reduction is possible if too many babies are conceived - one or more of the fetuses is removed. Couples will have to consider the ethical and emotional aspects of this procedure.

• Surgical procedures for women
  
  
  • Fallopian tube surgery - if the fallopian tubes are blocked or scarred surgery may repair them, making it easier for eggs to pass through them.
  
  
  • Laparoscopic surgery - a small incision is made in the woman's abdomen. A thin, flexible microscope with a light at the end (laparoscope) is inserted through the incision. The doctor can then look at internal organs, take samples and perform small operations. For women with endometriosis, laparoscopy removes implants and scar tissue, reducing pain and often aiding fertility.

Assisted conception

• IUI (intrauterine insemination) - a fine catheter is inserted through the cervix into the uterus to place a sperm sample directly into the uterus. The sperm is washed in a fluid and the best specimens are selected. This procedure must be done when ovulation occurs. The woman may be given a low dose of ovary stimulating hormones.
  
  IUI is more commonly done when the man has a low sperm count, decreased sperm motility, or when infertility does not have an identifiable cause. The procedure is also helpful for males suffering from severe erectile dysfunction.


• IVF (in vitro fertilization) - sperm are placed with unfertilized eggs in a Petri dish; the aim is fertilization of the eggs. The embryo is then placed in the uterus to begin a pregnancy. Someitmes the embryo is frozen for future use (cryopreserved). Louise Joy Brown, born in England in 1978, was the world's first IVF baby. Before IVF is done the female takes fertility drugs to encourage the ovaries to produce more eggs than normal.
  
  Time-lapse imaging triples the chances of having a baby for couples undergoing IVF treatment, researchers reported in Reproductive BioMedicine Online (May 2013 issue). Described as a "major breakthrough", time-lapse imaging became available in 2013 in the UK for monitoring the development of IVF embryos before they are implanted in the womb.
  
  In an Abstract in the journal, the authors wrote "Time-lapse imaging of human preimplantation IVF embryos has enabled objective algorithms based on novel observations of development (morphokinetics) to be used for clinical selection of embryos."
  
  With this new technique, the scientists could develop a way of accurately identifying which embryos are more likely to have aneuploidy (abnormal chromosomes). Embryos with aneuploidy are much less likely to be successfully implanted.
  
  The researchers, from CARE Fertility, said further large-scale studies are needed to confirm their findings.
  
  Researchers from Mount Sinai Hospital in Toronto, Canada, reported in CMAJ that IVF is more successful if the woman has sufficient levels of vitamin D.


• ICSI (Intracytoplasmic sperm injection) - a single sperm is injected into an egg to achieve fertilization during an IVF procedure. The likelihood of fertilization improves significantly for men with low sperm concentrations.


• Donation of sperm or egg - if there is either no sperm or egg in one of the partners it is possible to receive sperm or eggs from a donor. Fertility treatment with donor eggs is usually done using IVF. In the UK and a growing number of countries the egg donor can no longer remain anonymous - the offspring can legally trace his/her biological parent when reaching the age of 18.


• Assisted hatching - this improves the chances of the embryo's implantation; attaching to the wall of the uterus. The embryologist opens a small hole in the outer membrane of the embryo, known as the zona pellucid. The opening improves the ability of the embryo to leave its shell and implant into the uterine lining. Patients who benefit from assistant hatching include women with previous IVF failure, poor embryo growth rate, and older women. In some women, particularly older women, the membrane is hardened, making it difficult for the embryo to hatch and implant.


• Electric or vibratory stimulation to achieve ejaculation - ejaculation is acheived with electric or vibratory stimulation. This procedure is useful for men who cannot ejaculate normally, such as those with a spinal cord injury.


• Surgical sperm aspiration - the sperm is removed from part of the male reproductive tract, such as the vas deference, testicle or epididymis.

Complications of infertility treatment?

• Ovarian hyperstimulation syndrome (OHSS)
  
  The ovaries become very swollen, leaking excess fluid into the body. The ovaries produce too many follicles (small fluid sacs in which an egg develops). OHSS usually occurs as a result of taking medications to stimulate the ovaries, such as clomifene and gonadtrophins, and can also develop after IVF. Symptoms can include:
  
  
  • Bloating
  • Constipation
  • Dark urine
  • Diarrhea
  • Nausea
  • Pain in the abdomen
  • Vomiting
  
  In most cases symptoms are mild and easy to treat. On very rare occasions the patient may develop a blood clot (thrombosis) in an artery or vein, liver or kidney problems, and respiratory distress. In very severe cases OHSS can be potentially fatal.


• Ectopic pregnancy
  
  This is a pregnancy when the fertilized egg does not implant in the womb - in most cases the fertilized egg grows in the fallopian tube. If it stays in the fallopian tube the mother will usually miscarry before complications develop, such as the rupture of the fallopian tube. Women receiving fertility treatment have a slightly higher risk of having an ectopic pregnancy. An ultrasound scan can detect an ectopic pregnancy.


• Coping mentally
  
  As it is impossible to know how long treatment will go on for and how successful it will be, coping and persevering can be stressful. The emotional toll on both partners might be considerable and can have an impact on their relationship. Some people find that joining a support group helps - being able to talk to others who share similar problems, aspirations and anxieties can be uplifting. It is important to tell your doctor if you are suffering mentally and/or emotionally. Most fertility doctors have access to counselors, as well as other people and professionals who can offer helpful support.