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Understanding Infertility

To get a proper understanding of infertility one needs to first understand the human reproduction system in detail and way it functions. Humans reproduce through fertilization of the sperm with an egg. For fertilization to occur, sperm must be deposited in the vagina within a few (5) days before or on the day of ovulation. Sperm transfer is accomplished by copulation.
However, often couples are unable to conceive even after having regular unprotected sex. This is referred to as infertility. This could be because of the biological inability of an individual to contribute to conception, or because the female cannot carry a pregnancy to full term. Men and women have different underlying reason that can make pregnancy not possible.

  • The male reproductive system consists of the testicles (the primary organ of generation), the duct system (epididymis and the vas deferens), the accessory glands (seminal vesicles and prostate gland), and the organ of sexual intercourse (penis). Each of these components are best be understood by reference to the figures.

    Male Reproductive System

  • Testis: is the male gonad (organ of generation) – It produces millions of sperms – the male germ cell (also called the male gamete). The testis is an oval shaped organ, lodged in a bag of wrinkled skin called scrotal sac which is seen hanging between the upper thighs. The testis is present one on each side of the midline in the scrotum. Being outside the abdomen, the temperature of the scrotum is 20 to 30 lesser than the normal body temperature; this is ideal for growth and maturation of sperms. Sperms are produced inside tiny coiled tubes called seminiferous tubules. These sperms mix with other secretions of the male reproductive system (seminal vesicle and prostate) to form a fluid called the semen. Besides sperms, the testis produces a hormone called testosterone (the male sex hormone). This hormone is released directly into the blood. Testosterone maintains typical male sexual characteristics like deep voice, largemanly muscles, body and facial hair, and it also stimulates the production of sperm.

  • Epididymis: Sperms are collected by the epididymis, a comma shaped organ above the testis. The sperms undergo functional maturation here.

  • Spermatic cord: The epididymis transfers the sperms to the spermatic cord which is also called the vas deferens. Vasectomy is a surgical procedure wherein the spermatic cord is cut and tied on both sides. This is done for sterilization of the male. The spermatic cord conveys the combined secretions of testis and epididymis to the urethra. In the male, the urethra is a common passage for both semen and urine.
    Seminal vesicle: Two leaf shaped organs are located at the back of the urinary bladder. Their ducts join the spermatic cord to jointly open into the urethra. The seminal vesicle contributes a large volume of fluid to the semen.
  • Prostate: This is a chestnut sized gland located below the urinary bladder and surrounds the beginning of the urethra. Along with the seminal vesicle, it contributes to the semen. This gland often enlarges in old age and may obstruct the flow of urine, sometimes resulting in an emergency.
  • Urethra and penis: The greater part of the urethra is located in the penis. The penis is a long tubular organ located at the lower part of the abdomen in front of the scrotum. It is the male organ of copulation (sexual intercourse). During peak sexual stimulation (orgasm), semen is released into the female genital tract through the penis. This release is called ejaculation and the semen that comes out is called the ejaculate. The penis is endowed with special tissue which make it erect during sexual activity (erectile tissue). During non sexual activity, the urethra deep inside it transports urine to the outside. The tip of the penis is a bulbous expansion called glans penis. This is a very sensitive part of the penis (like the clitoris in female) and is covered by foreskin called prepuce. The foreskin is removed during a procedure called circumcision. The rest of the penis is called the shaft. In the male the urethra transports both the semen as well as urine – either of the two at a time.
    The penis, scrotum and the immediately adjacent areas are called the male external genitalia – the visible part of the male reproductive system.
  • In the males, the hypothalamus produces releasing hormones (Gonadotrophic releasing hormones GnRH) similar to that of the female. This induces the pituitary gland to release LH (luteinizing hormone) and FSH (follicular stimulating hormone – more appropriately called interstitial cell stimulating hormone – ICSH). However, the effect of these hormones is on the testis. FSH maintains the production of sperms (produced and released in millions, unlike the ovum which is released one per cycle ). LH stimulates the production of testosterone, the male sex hormone. Testosterone maintains the male sexual characters. Feedback loops exist with the pituitary and the hypothalamus so that the levels of these hormones are kept well balanced.

    hypothalamus

  • Semen is a pooled secretion from all glands of the male reproductive system i.e. testis, epididymis, seminal vesicle and prostate. While testis contributes the sperm, the other organs contribute the fluid medium for the sperm to survive, derive nutrition, move and reach the female reproductive system. It also provides lubrication for the duct system. Hence examination of the semen will be an important aspect of investigation of a case of male infertility. At the peak of sexual intercourse or during the peak of masturbation (called orgasm), the semen is released by the male. The penis is maintained erect during this state and the urine flow from the bladder is temporarily blocked till the sexual act is completed.

The female reproductive system is largely restricted to the pelvic cavity with the exception of the breast. It consists of:

  • Ovary: The primary organ of formation of female germ cell (ovum) is the ovary. There are two ovaries located in the upper part of the pelvis behind the fallopian tubes. During the fertile period of the woman it produces one ovum per ovarian cycle. Besides this it releases hormones estrogen and progesterone which drives the uterine cycle.
    Female Reproductive System
  • Uterus: A single uterus is located in the midline and is the organ for anchoring the developing conceptus in the event of pregnancy.
  • The uterus is shaped like an inverted pear and consistsof body, a fundus above this and a cervix below that opens into the vagina. The cervix is a narrow cylinder connecting the uterine body with the vaginal cavity.
  • •The uterus is a thick muscular bag strong enough to carry the developing baby till delivery. Powerful contractions of the muscles of the uterus expel the baby during delivery.
  • Its inner wall (endometrium) has provision for adequate blood and nutrition for the developing baby.
  • In the non-pregnant state the mucosal lining is subject to variations during the menstrual cycle, secondary to influence of ovarian hormones. The proliferative and secretary stage are key stages in this cycle, with the cyclical menstrual flow occurring at the end of the secretary stage.
  • The vagina is the female organ of copulation. It extends from the external genitals (vulva) to the uterus. It receives the penis – the male organ of copulation during intercourse. Semen from the male is deposited here and the sperms make their way up into the uterus through the cervix. During each cycle, the menstrual blood and debris from the uterus is released to the outside through the vagina.
  • The external genitalia of the female are the visible parts of the female reproductive system along with the breast. It is a triangular area located in the lower part of the pelvis and between the legs. It consists of the labia majora, labia minora, clitoris with its protective hood, the prepuce, introitus and remnants of hymen. The introitus leads to the vagina (See figure).
  • The breast (mammary glands) are present in both sexes, but enlarges in females to become a prominent part of the female chest during puberty (10 to 12 years of age) and remains enlarged for her entire lifetime thereafter. It is a soft rounded elevation, one on either sides of the midline in the chest. At its summit is a dark brown patch of skin with a nipple into which the ducts from the milk glands empty. It is an accessory organ of the female reproductive system. It is made of milk secreting glands. These glands further grow during pregnancy and become functional (secrete milk) during delivery and in the post pregnancy period. Mother’s breast milk is the ideal source of nutrition for the new born for the first three months. The breast is also influenced by the normal ovarian cycle
    Female Breast

  • There are several other organs and systems in the body which control and coordinate the male and female reproductive systems. Notable of these are the endocrine and nervous systems. The pituitary gland is the master endocrine gland of the body and controls all the other endocrine glands in some way or other. It is located inside the brain box, just behind the nose. In turn, it is connected to the hypothalamus of the brain. The hypothalamus controls the pituitary gland. Hence, the hypothalamus can be considered the head of the neuro-endocrine orchestra which controls the entire body. The important endocrine glands are thyroid,adrenal, pancreas, testis and ovary. The thyroid gland is located in the neck, right in front of the windpipe (trachea). The adrenal is located on the top of the kidney (one each).

    Hormone Glands

  • The hypothalamus releases Gonadotrophin releasing hormone (GnRH). The pituitary releases follicle stimulating hormone (FSH) and leuteinising hormone (LH). The ovary releases oestrogen and progesterone. Release of these hormones are interlinked and controlled by feedback loops which finally run a successful ovarian and uterine cycle. In simple terms, we call one uterine cycle as one menstrual cycle. In women, it takes an average of 28 days for one menstrual cycle to be completed. The periodicity is indicated by passing of blood (the monthly periods) through the vagina.
    Hormone Glands

    There exists two cycles in the female reproductive system – ovarian and uterine.

  • The ovarian cycle is designed to release one ovum per cycle. The ovary has in stock several thousand ova – enough to last the entire reproductive life of the female. Each is stored in a small island called the ovarian follicle. However, during each cycle, a few ovarian follicles undergo maturation, until only one follicle from one of the ovaries reach a ripe stage (called the Graafian follicle) to release one ovum. This is called ovulation. The ovum (also called egg) is picked up immediately by the finger like end of the fallopian tube (uterine tube) and slowly propelled towards the uterus. It is here (ampulla) that the fertilization takes place. Sperms swim across the cervix and body of the uterus and reach this site.
    The FSH secreted by the pituitary gland stimulates the follicles of the ovary to ripen and produce estrogen. This occurs for about 14 days from the first day of the periods (menses). The first day of the menses is a good indicator of the cycle since bleeding is obvious and it is easy to maintain a calendar of progress.

    Ovarian Cycle

    By about the 14the day LH from the pituitary stimulates the ovary to produce progesterone. Ostrogen production continues.
    It is also around this time (mid-cycle) that the ovary releases one ovum. Although several follicles ripen in both ovaries, only one reaches completion (from only one of the ovaries) and releases the ovum. LH causes a slight rise in basal body temperature on day 2 after ovulation and therefore can be a rough indicator that ovulation has occurred. This is measured by a domestic thermometer and the reading is taken from the mouth early in the morning just at wake up.
    Hence the ovarian cycle can be divided into a pre-ovulatory or follicular phase and a post ovulatory or luteal phase.

    Basal Body

    During its course through the fallopian tube, there is a good chance that the ovum can be fertilised by the sperm. Hence forconception to occur, the couple must time their sexual intercourse to coincide with this period i.e. 1 day prior and 5 days after the day 14 of the menstrual period (day 14 also included). This is calculated considering that the sperms can survive for upto 5 days in the female genital tract. Hence a good timing may be an important strategy for achieving conception.

    Body Temperature

    In the event of a successful sexual intercourse, several sperms of the male will swim through the uterus and enter the fallopian tube. Here one of the sperms will fuse with (fertilises) the ovum. This results in the conceptus (baby ) and the sequence of events is the pregnancy.

    Ovarian Cycle

    However, if the fertilization does not occur, the uterus will shed its endometrium within the next 2 weeks; this results in the menstrual flow. After ovulation, the left over cells of the ovarian follicle convert into a structure called corpus luteum. This has a short life span during which it secretes oestrogen and progesterone. These hormones get the uterus ready for the fertilized egg to be implanted soon. By about 24th – 26th day of the cycle, the hormones are produced in very low levels. The uterus reacts in the next two days by shedding off its inner lining (endometrium). This is referred to as monthly bleeding or menses. As the hormone levels fall, the female undergoes a stage called premenstrual tension. This is reflected as anxiety, irritability, headache, mood swings, pelvic discomfort, muscle cramps, bloating, constipation, swelling and tenderness of the breasts.
    Menses is an indication that the uterine cycle is running actively and pregnancy has not occurred. Cessation of menstrual periodsin a sexually active female is a strong indication of pregnancy and tests may be undertaken to confirm this. In the event of pregnancy, the uterine endometrium will develop further to receive the fertilised egg and provide nutrition and support to the growing baby.

    Uterine cycle:
    The uterine cycle closely parallels the ovarian cycle and is in fact driven by the ovarian hormones. In a 28 day menstrual cycle, let us consider the first day of bleeding (menses) as day 1 of the cycle. Menses is the shedding of the inner lining of the womb and is called the endometrium. It is noticed by the female as bloody discharge for about 5 days. The next 9 days are characterised by proliferation of glands and blood vessels. Hence, this phase of 14 days (5 plus 9) is called the proliferative phase – it parallels the pre-ovulatory phase of the ovarian cycle. It is chiefly controlled by the estrogen produced by the ovary.

    Uterine Cycle

    From day 15 to day 28 (secretary phase) the uterus parallels the luteal phase of the ovarian cycle and is characterised by secretion from the glands; there is also an increase in blood supply. The endometrium becomes rich in glycogen. This phase is designed by nature to keep the uterus ready for receiving the baby. In the event of pregnancy, the phase continues into full-fledged pregnancy. In the absence of pregnancy, the uterus is slowly removed from the influence of the progesterone and sheds its endometrium at the end of the cycle (end of 28th day). Thereafter the next cycle commences. Hence, the female reproductive system is designed to release one ovum per cycle, enable fertilization thereafter and subsequently to host the developing baby in the uterus. Cycles are programmed to repeat in the absence of pregnancy. The male reproductive system, on the other hand continuously produces sperms in numbers counted in millions. The male is ready to impregnate a female with sperms almost anytime (except when he has released sperms less than 24 hours earlier).

The only way to achieve pregnancy in the normal process is through frequent unprotected sexual union with your partner. By this we mean actual penetration of the male penis into the female vagina, followed by release of semen into her.

What happens during sexual union: The friction caused by moving his penis in and out of her vagina will cause both the partners to get increasingly excited until eventually he ejaculates (or ‘comes’) and releases a sticky white substance called semen. Semen contains millions of sperms – the male germ cells. These sperms swim up the woman’s vagina, into her uterus (womb) and then into her fallopian tubes where they may join with the tiny egg that she releases from one of her ovaries every month. If this ‘union’ (also known as fertilisation or conception) occurs, then she will become pregnant.

Ovulation window: The most important point to be noted is that sex must take place around the time the female partner is ovulating. During this time, the sperms will swim through her reproductive tract and reach the ovum where fertilization takes place (union of the ovum and sperm; see figure). Ovulation occurs approximately on the 14th day after the previous mensus (counted from the first day of the previous mensus). Since this date can be variable, it is best to have frequent sex during the period when the female partner is not menstruating. In general two to three days of sex per week is recommended. More frequent the sexual union, higher the chances of achieving pregnancy. Once fertilization has taken place the ovum does not allow any other sperm to enter it. Hence subsequent sex on the following days will have no dangerous effect on the developing embryo. However it is better to be gentle in lovemaking if a couple is planning for pregnancy.

Importance of conception:

  • Conception is the fusion of the male (sperm) and female (ovum) germ cells which results in the formation of an embryo (also called zygote or conceptus which means baby in its tiniest form). In humans, direct division of the egg, without fertilization is not possible. Hence unprotected sexual intercourse with release of sperms into the female genital tract is essential for pregnancy to occur in the normal course of events. conception_readies
  • Conception readies the uterus to develop to receive and support the embryo for the next nine months of pregnancy.
  • Before conception both the egg and sperm have only one half of the total genetic requirement for the conceptus i.e. each partner germ cell has 22+1 or 23 chromosomes. With conception, both the male and female chromosomes mix to restore the normal 46 chromosomes required for human beings.
  • Of the 22+1 chromosomes mentioned above the 22 chromosomes are identical in both partners while the 23rd chromosome is different. In the male it is called the Y chromosome and in the female it is called the X chromosome.
  • During fusion, if the pairing results in XX formation, the resulting sex of the child is female. On the other hand if the pairing results in XY formation, the resulting sex of the child is male. Hence, conception also decides the sex of the baby. A male baby will have the genetic constitution of 22 XY, while a female baby will have 22 XX.
  • Since the conception results in each partner contributing one half of the total chromosome content, the baby will be a genetic mirror of both the partners.
  • Conception stops the ovarian and uterine cycle till pregnancy is completed. Ovarian and uterine cycles continue to be blocked for a few months after pregnancy when the mother is actively lactating. Slowly however, the cycles start returning and the normal monthly pattern is restored.
  • The baby is a living memento of the process of conception and it belongs to both the biological partners. Hence, the bondage between the couple as well as with the baby enhances familial bliss.
  • From the point of conception, the embryo grows rapidly from two-cell to four-cell, then four-cell to eight-cell and so on until it forms a mass of cells called morula (about 16 cells).
  • Events following conception in the female:

  • As cell division progresses and more cells are formed, the size of the cells reduces. A cavity is then formed inside and hereafter the embryo is called blastula (about 32 cell stage).
  • Slowly the embryo is rolled into the uterus by tiny hair like structures (called cilia) of the fallopian tube. By about the 6th or 7th day it would have reached the uterus.
  • The fertilized egg sheds its protective covering around it (called zonapellucida) and this triggers the surface cells to stick to the uterine lining.
  • fertilization

  • This sticking establishes the first contact of the embryo with the mother’s endometrium. In due course it breaches into the blood vessels of the endometrium and a nutritional interface between the two is formed. This is called the placenta. In the course of the pregnancy, the placenta grows into a large structure and maintains contact with the baby through the umbilical cord. During delivery, after the baby is born, the placenta is delivered in the next few minutes.
    Placenta
  • The other cells (excluding the surface cells) form the embryo proper. It divides into three germ layers called ectoderm, endoderm and mesoderm. All the parts of the baby are formed from one or more of the three germ layers.
    sperm_fertilizing
  • Maximising fertility:

  • Prediction of ovulation: There are several methods from morning temperature estimation (basal body temperature) to hormonal tests (ovulation predictor kits) to predict ovulation. To maximise fertility have sex frequently, even daily during the ovulatory period.
  • ovulates

  • Pre-conceptual planning: Make pregnancy a planned event. Discuss with your partner and take a decision together.
  • The female partner can get a general check-up as well as an obstetrical examination done to ensure her reproductive system is normal. Similarly, the male partner can have a general and andrologicalcheck-up. Contact Manipal Fertility for details. Folic acid is recommended during the period when you are conceiving. Your doctor will give you the right prescription.
  • Maintain a healthy lifestyle. Maintain a healthy weight and exercise regime. Reduce stressful work so that you are ready for the coming pregnancy.
  • Stop smoking and avoid caffeine and alcohol. Do not take any medications during conception time without consulting the doctor. Most important, avoid over-the-counter medications.
  • Do not use over-the-counter vaginal lubricants, including K-Y Jelly as these can decrease fertility. Do not use saliva for lubrication. If you need a lubricant, ask your doctor for the right prescription.
  • For the male partner:

  • The role of the male partner is to give his wife the comfort and confidence to go through the pregnancy. Besides, he himself must be in good health. His sperms must be of good quality. With evidence showing that stress and environmental factors affect sperm quality, the male partner must be cautious to maintain a stress free work atmosphere congenial with good sexual health.
  • Natural sexual activity:

  • When the sperm analysis is normal, there is no significant ovarian dysfunction and any obstruction of the fallopian tubes is not suspected, natural sexual activity is recommended.
  • Natural sexual intercourse is primarily meant for reproduction, although it also provides a pleasurable experience to the partners and is considered as an expression of love.
  • Besides reproductive function, sexual intercourse provides strong emotional bonding between the couples and establishes a long lasting relationship.
  • A female ovulates on the 14th day of a normal cycle. After ovulation the egg is viable for 24 hours – the sperm must fertilize it within this time. Otherwise the ovum degenerates and a fresh ovarian cycle begins. Sperms can survive in the female genital tract for upto 5 days. Hence, there exists a fertility window for the couple. Sex during this time is most likely to end in a successful pregnancy. Sexual intercourse can therefore be attempted with a clearly timed approach. Unprotected sex is recommended from one day prior to – up to 5 days after the expected date of ovulation.
  • It has to be remembered that the human female ovulates internally and hence it is not obvious either to her or her partner. A couple desirous of a child have to rely entirely on the probable date of ovulation which is difficult to predict. However, several recent technological advances are helpful for the couple to confidently know the ovulation window.
  • The basal body temperature rises by half to 1 degree during ovulation. This can be measured on a daily basis using a thermometer every morning as you wake up.
  • Ovulation predictor kits are now available in medical shops. These estimate LH levels and can predict ovulation 24 to 36 hours in advance.
  • The cervix of the uterus secretes mucous which vary in quality and quantity during the different stages of the cycle. During ovulation it is clear and more watery in nature. A film of mucous is found to stretch when held between the thumb and the forefinger. This mucous is receptive to the entry of sperm into the uterus. At other times the mucous is thicker.
  • During ovulation, most women may feel dampness in the genitals.
  • The sexual desire and drive is stronger during this time.
  • Ultrasound may be of help to track the uterus and ovary so that the exact ovulation window can be predicted.
  • Stimulated cycle sexual activity: As a part of the management of infertility, it may be necessary to use certain medicines to mimic or actually direct an ovarian cycle in a normal pattern. This is called stimulated cycle sexual activity. Ovulation inducing drugs are given to the female partner. Sex between the partners is advised appropriately depending on the timing of ovulation.

  • Clomiphine citrate is given in a tablet form to induce follicular development and ovulation. Successful pregnancy may not occur during the first cycle and the couple may need to be mentally prepared for trials of a few more cycles. Nearly 45 % of the couples end in successful conception by the 6th cycle.
  • FSH is given as an injection for a fairly long period (days or weeks). When the follicles are noted to be maturing to the right stage (checked with regular ultrasound monitoring), hCG (human chorionic gonadotrophin) is given as an injection to trigger ovulation.

Most couples of typical child bearing age are able to achieve a pregnancy within one year if they have intercourse twice per week or more often without using any birth control. Some couples experience difficulty in conceiving even after one year of trying. When pregnancy is this slow to occur, the condition is termed as infertility. Infertility can occur because of problems with the male partner or the female partner or both. A few cases could also be an unexplained infertility.
If a couple are trying to get pregnant for more than one year (or six months if they are 35 years or older) and have not been successful, a series of tests will be needed to identify the cause of infertility. The ovary, uterus and the fallopian tubes of the female as well as the sperm of the corresponding male partner, and possible blood tests in both to check for hormonal problems may be necessary.
Male factor infertility refers to the failure of a couple to achieve conception due to problems specifically related to the man’s sperm, seminal fluid, or male reproductive organs. Similarly, if the reason for failure to conceive lies with the woman, it is referred to as female factor infertility.
Infertility and its causes may be different for each couple. During the last decade, medical science has made great strides in the ability to diagnose and treat infertility. Roughly two out of three of couples who seek medical intervention are able to give birth successfully and become happy parents.

  • Once you have decided to have a child, try unprotected sex for one year if the female partner is 30 years or less in age and the male partner is healthy.
  • A doctor’s consultancy is recommended if the female partner is 35 years or more in age, or if one of the partners has a known or suspected fertility problem.
  • Note that sub fertility is a problem that can affect both the partners and for most of the problems, treatment is available.
  • A fertility clinic like Manipal Fertility provides a comprehensive care for both partners under one roof. The female partner will be treated by a gynaecologist and the male partner will be treated by a urologist or Andrologist.

Check list for a probable conception:


For men:

  • Anatomically normal male reproductive systems with no congenital abnormalities.
  • Normal sperm production of sperms in quality and quantity.
  • No blockage of the tubes through which the semen is transported (epididymis, vas deferens, ejaculatory duct, urethra).
  • Normal erection
  • Normal hormonal balance to coordinate the sexual process.
  • Overall normal family history with no major genetic problems.
  • No major illness or life styles that may affect the sexual process and in particular no genitourinary disorders.

For women:

A normal female reproductive anatomy.

Normal functioning ovarian and urterine cycle with regular monthly release of a normal good ovum. Good coordination from the pituitary gland and hypothalamus.

No disease or blockage in the transport pathway of the ovum ( normal patent fallopian tube).

Normal urterine endometrium where the fetus will be finally lodged.

Age at conception: preferably below 30.

Normal family history with no major genetic problems.

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