INTRODUCTION

What is Infertility?

  • Infertility is defined as failure to conceive after one year of unprotected intercourse.
  • If woman’s age is more than 35 years then this period is 6 months.
  • Out of all etilogical factors, male factor contributes for almost 35-40%.
  • Female factor contributes for 30%.
  • Unexplained infertility is term defined as in which all the investigations of both the partners are normal, but couple fail to conceive.

Male Sub Fertility

The reduced number of semen production is one of the predominant causes of infertility in males.

  • Semen may contain few spermatozoa (oligozoospermia) or no spermatozoa (azoospermia) due to problems in its production in the testicles. The prominent causes for low semen production are due to:
  • Disorder of the brain glands (Hypophysis and Hypothalamus that generate the hormones regulating the formation of spermatozoa)
  • Genetic disorders (Klinefelter syndrome, alteration of genes contained in the Y-chromosome that regulates the formation of spermatozoa
  • Numerous testicular problems, such as underdevelopment, anomalous development, failure to descend into the scrotum (cryptorchidism), trauma, and inflammations (whether sexually transmitted or otherwise), tumors, exposure to toxic substances, chemotherapy and radiotherapy and varicocele
  • Unexplained infertility is term defined as in which all the investigations of both the partners are normal, but couple fail to conceive.

Spermatozoa may not be found or found in very low numbers in semen because of the obstructions in their path from the testicles to the urethra owing to various reasons.
They are

Absence of part of the conduits (frequently associated with the cystic fibrosis gene)

Spermatozoa can also show anomalies in their

  • Inflammations
  • Tumors
  • Trauma
  • Involuntary surgical lesions
  • Involuntary surgical lesions
  • Involuntary surgical lesions
  • Involuntary surgical lesions
  • Vasectomy
  • Motility(asthenozoospermia),
  • Shape(teratozoospermia)
  • vitality(necrozoospermia) due to different causes relating to infections, presence of antibodies(which act against spermatozoa),
  • DNA fragmentation(genetic material contained in the spermatozoid’s head),
  • oxidation phenomena, varicocele(anomalous dilation of veins that come out mainly from the left testicle).

The quality and count of the sperms can also be affected by major diseases such as diabetes, thyroid disorders, kidney disease and hepatic insufficiency, as well as the intake of certain medications, tobacco and stress.

Genital tract disorders

Genital tract disorders stop semen from being deposited in the vagina during intercourse (erectile impotence, absence of ejaculation).

  • In addition, there could be an abnormal situation of the urinary meatus like
  • If it is below its normal location (hypospadias) or above it (epispadias)
  • If the penis has a curvature that is too pronounced or a decrease in its size
  • Other general problems are Obesity and other erection problems, premature or delayed ejaculation and other ejaculation problems that can also prevent the spermatozoa from being adequately deposited in the vagina.

Male Infertility

Semen Analysis:

Semen analysis is gold standard test to see the severity of male infertility.

Normal reference value:

Oligo (Less Count)

  • Lowest normal reference value where 5% of population getting pregnancy is
  • Count: 15 million
  • Motility (Forward progressive): 32%
  • Morphology: 4%
  • DNA Fragmentation: 70 % (N) atleast
  • Mild oligo 10-15 mil
  • Moderate oligo 5-10 mil
  • Severe oligo: < 5 mil

Astheno (Low motility)

DNA Fragmentation index:

  • Mild: 20-32%
  • Moderate: 5-10mil
  • Severe: <10%
  • <15% can able to conceive naturally
  • 15-25% antioxidant + IUI
  • >30% IVF & ICSI .

DNA Fragmentation index:

  • DNA Fragmentation index indicates beyond count & motility.
  • It directly or indirectly indicate the power of sperm or ability of a sperm to fertile egg.
  • It is quantitative & qualitative estimation of semen.

Female Infertility

EtiologIcal Factors

Ovarian Factors

Anovulation:

Anovulation is a state in which ovulation is absent.

  • This is a result of hormonal imbalance or due to the improper development of the ovaries.
  • This is when the formation of the ovum (egg) in the ovary is disturbed. Approximately, 35% of women experience anovulation.
  • The most known cause of this abnormality is the polycystic ovarian syndrome (PCOS). Polycystic Ovarian Syndrome (PCOS) is a hormonal disorder that causes irregular menstrual cycles or lack of menstruation (amenorrhea), obesity and features of hyperandrogenism like acne and hirsutism.
  • The origin of this hormonal disorder may be in the hypothalamus, pituitary gland, or in the ovary itself.

The initiation of the treatment involves restoring weight and lifestyle changes.If normalization of menstrual cycle and ovulation is not achieved, the next step is medical treatment with medications or injectable hormones to normalize the hormonal functions and stimulate ovulation.

  • Ovarian drilling (making small holes on the ovary’s surface by using heat or laser) is also considered to improve the ovarian hormonal microenvironment.

Pathological factors Endometriosis

Endometriosis is a state when the tissue that lines the uterus also grows outside in organs like the ovaries, fallopian tubes, bladder and peritoneum.

  • Women who are affected with endometriosis show symptoms of increasingly painful menstruation (dysmenorrhea), menstruation that is abnormal in intensity (whether heavy or light), pain during sexual intercourse (coitalgia) and infertility.
  • Endometriosis can also cause blood cysts in the ovaries. Endometriosis might also be caused by the effect on the tubes’ functionality, which is caused by the inflammatory and wound-healing component of the endometrial tissue. However, the presence of a family hereditary factor and the possibility of poor oocyte quality might also be responsible. Nearly 35% of infertile women suffer from endometriosis.
  • Surgical treatment by laparoscopy (diathermy/argon/excision) is usually prescribed to improve the patient’s fertility.

Tubal Factors

Between 20-25 percent of all cases of infertility are related to tubal factor.

  • Tubal factor infertility includes cases of either blocked fallopian tubes or partially blocked fallopian tubes, one of the two tubes blocked, tubal scarring and other types of damage to the fallopian tubes.
  • The result of endometriosis, PCOS, tubal factor infertility is a prominent factor in problems of infertility in women.
  • Scar tissue formed by endometrial tissue, surgery, or cysts also create long-term difficulties when it comes to conception.
  • Sometimes the tubal damage is not very serious. Nevertheless, when after standard fertility testing is performed there is no other obvious cause of infertility found, it is generally attributed to tubal factor infertility. Where cases of minimal scarring are found, a diagnosis of unexplained infertility is given.

Primary Cause of Tubal Factor Infertility

  • The primary cause of tubal factor infertility is pelvic inflammatory disease which is generally caused by either gonorrhea or Chlamydia infection that has travelled from the cervix through the uterus and into the fallopian tubes.
  • As the body releases white blood cells to combat the infection, the tubes fill with pus and the bacteria are either brought under control or they are destroyed. Sadly, the carnage that is associated with this battle is the destruction of the inner lining of the tubes, which become permanently scarred. The end of the tube or tubes may become blocked with scar tissue as can the ovaries. Damage may be minimized if the infection is caught early enough and treated aggressively with antibiotics.

Tubo-peritoneal factors:

  • Fallopian tubes function as an integral part in the reproduction process. The Fallopian tubes pick up the ovum released during ovulation, transport the spermatozoa towards the ovum and carry the fertilized ovum to the uterus. Damage to the Fallopian tubes will interfere in these vital functions and hence, prevent pregnancy. The tubo-peritoneal factor can cause an ectopic pregnancy (pregnancy in the Fallopian tube).
  • Tubal damage can occur due to: Genital tuberculosis & Infections arising from the uterine cervix or (Pelvic Inflammatory Disease, PID).
  • The bacterial infections involved with PID are Gonorrhea and Chlamydia which produce an inflammatory reaction causing scarring and fibrosis that prevents the proper functioning of the Fallopian tubes.Infections arising from the abdominal cavity, e.g. Appendicitis
  • The Fallopian tube gets filled with inflammatory fluids and thus, becomes a potential source of chronic infections which results in Hydrosalpinx.
  • Tubal damage can be treated by endoscopic surgery, tubal microsurgery and ART techniques like IVF/ICSI.

Uterine Factors

  • In general cases, the embryo implants in the uterine cavity, so if the cavity has fibroids, polyps or adhesions inside it, the embryo will fail to implant.
  • In addition, some women may be born with anomalies of the uterine cavity like an intrauterine septum or bicornuate uterus .
  • The miscarriage rate among women with a large uterine septum is quite high.
  • Fortunately the majority of the above conditions can be resected or corrected surgically and is usually followed by a subsequently normal implantation rat.

Infertility & Obesity

  • Obesity may be defined as a body mass index (BMI) of 30 or higher.
  • It is a medical condition in which excess body fat builds up to the extent that the health of the individual becomes negatively affected.
  • It is becoming increasingly common in both men and women in Western developed nations, including Australia and the US, and exerts significant financial pressure on health care systems.
  • Obesity is usually not caused by a single factor, although the genetic make-up of a person can influence the probability of developing the condition. The most significant contribution to the rise in obesity is thought to be the changes in behaviour and environment seen in modern society as a result of technological advances. In particular, the reduction in physical activity levels has been put forward as a major contributing factor in the development of the disease.

How is obesity related to fertility?

It is now known that obesity is associated with a general decline in overall fertility, with a significant relationship existing between excess body fat and problems with reproduction. It is therefore becoming increasingly that important in Western nations to understand this association because of the steadily rising rates of obesity in these societies.

Male obesity and fertility

Little research has been carried out on male fertility compared to the vast amount of research done on female fertility. However, some studies indicate that the degree of male obesity has a direct effect on oestrogen levels, with increased fat deposits corresponding to higher oestrogen and lower testosterone levels. These elevated oestrogen levels in men tend to suppress fertility because they prevent the synthesis of androgens (hormones required for the development and maintenance of normal male reproductive function).

Female obesity and fertility
Fertility issues arising from obesity in women include:

  • Irregular menstrual cycles,
  • Problems with ovulation,
  • Increased androgen levels
  • Polycystic ovarian syndrome (PCOS),
  • Decreased success rates with assisted reproductive technologies (ART)
  • Increased risk of miscarriage

These associations between obesity and reduced fertility are particularly significant when excess fat is deposited around the abdominal area.

  • Changes in circulating sex hormones are thought to be largely responsible for decreasing fertility. The overall effect of these changes is usually an increased production of androgens, leading to a condition called hyperandrogenism (excessive androgen production).
  • This condition is evident in obese women who experience amenorrhoea.

Obesity is also often associated with increased insulin production and insulin resistance. These two factors are believed to contribute to hyperandrogenism in obesity because insulin is important for the regulation of sex hormone production. This can be seen in obese women with PCOS, where excess weight gain leads to excessive insulin production, promoting increased androgen secretion and abnormal follicles in the ovary. This results in an overall disruption in ovarian and menstrual activity, causing fertility problems.

Obese women who turn to assisted reproductive technologies (ART) also face additional obstacles compared to non-obese patients. Obesity is linked to decreased success of fertility treatments such as in vitro fertilisation (IVF).

Infertility & Diabetes

The International Diabetes Federation estimates that there are 246 million adults with diabetes.

Anovulation is a state in which ovulation is absent.

  • In Type I diabetes the beta cells of the pancreas stop making insulin completely, so patients then have to inject themselves with insulin every day. Diabetes is an autoimmune disease and of all diabetics,
  • Type I affects between 5 – 10% of diabetics.

Type II often develops in people over the age of 40 years and is seen as a lifestyle disease. Diabetics diagnosed with Type II diabetes are often overweight and have been for some period of time. In the region of 80% of Type II diabetics are over weight.

  • Most of the Type II diabetes female patients are postmenopausal women, but with changing dietary and lifestyle patterns, the prevalence of obesity is increasing, so raising the incidence of Type II diabetes during the reproductive years therefore increasing diabetes and infertility problems.
  • There is a strong association between Type II diabetes and fertility, alterations in the length of the menstrual cycle, and the age of onset of menopause. This association may be explained by linking this disease to PCOS , the most common hormonal disorder among women of reproductive age, and a leading cause of infertility. Insulin resistance, obesity and diabetes mellitus strongly correlate with PCOS.
  • PCOS and Type II diabetes do have the same risk factors, such as hypertension, obesity, dyslipidemia and hyperinsulinemia. Hyperinsulinemia results from insulin resistance, which through alterations in the level of IGFBP (Insulin-like growth factor-binding protein) gene, IGF1 (Insulin-like growth factor 1) gene and SHBG (Sex hormone-binding globulin) stimulates increased androgen secretion at the adrenal gland and the ovary, subsequently causing anovulation. Legro et al.

Diabetes can affect fertility in many different ways.

  • In women with Type I diabetes, for instance, antibodies are produced that cause the woman’s body to attack the male sperm as well as her own eggs.
  • But diabetes also causes a general reduction in the function of the immune system making diabetics susceptible to various conditions. So is diabetes and infertility are linked, the evidence suggests that it is, what with Type II diabetic women having to deal with weight problems and PCOS, men having sexual problems such as erectile dysfunction, it certainly is linked, but it can be managed and solved, with following advice from your doctor .