Infertility Practice Sudhir R Shah, Beena N Trivedi, Dipal D Solanki, Manish R Pandya
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Complex Path Towards PregnancyChapter 1

 
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To understand the factors causing infertility, it is better to understand the anatomy and physiology of both female and male reproductive organs and the complex hormonal interaction which plays a primary role in producing and developing pregnancy.
 
In Females
The primary genital organs that play an important role for the occurrence of pregnancy are: Vagina, Uterus, Fallopian tubes and Ovaries.
 
Vagina
Vagina is hollow musculofibrous organ about 7 to 8 cm long, which communicates the exterior vulval region to the uterus at cervix. It has the capacity to expand and its mucous membrane reacts to hormones. Normally vaginal atmosphere is acidic.
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Fig. 1.1: Female genital organs
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Uterus
The uterus is pyriform hollow muscular organ situated in the pelvis. Uterus has body of the uterus and cervix at the lower most part. The inner lining of the uterus called endometrium is very sensitive to hormones and it plays an important role in menstruation and nidation of fertilized ovum.
Cervix is composed of fibrous connective tissue which is lined by columnar epithelium and secretary glands. It connects the vagina to body of the uterus. Cervical secretion plays an important role in reproductive events.
 
Fallopian Tubes
Fallopian tubes are paired structures measuring about 10 cm, starts from the cornual end of the uterus medially up to free open end laterally, on either side of uterus. It is divided in to four parts like Intramural, Isthmus, Ampulla and Infundibulum. The abdominal opening is surrounded by numbers of radiating fimbria. One of them is longer and attached to the outer part of ovary. Mucous membrane of the fallopian tube is ciliated. It helps in propagation of ovum, sperms and fertilized ovum along with the movements of the fallopian tube. Fertilization of mature ovum usually occurs in the outer third part of fallopian tube.
 
Ovaries
Ovaries are paired glands on each side of uterus and nearer to the fimbrial end of fallopian tubes. They are attached to the uterus through ovarian ligaments. It is 4the primary sex organ in female and produce hormones and releases the ovum under the control of hypothalamus and pituitary. Every month it releases a mature ovum, the event is called ovulation, which is picked up by fallopian tube. Ovaries are just like testes in male.
 
In Male
The primary genital organs playing an important role to achieve pregnancy are Testes, Epididymis, Vas deferens, Seminal vesicle, Prostate and Penis.
The testes are located in the scrotum, which consist of several layers of tissue. Functionally, the most important of the scrotal layers is a muscular coat formed by cremasteric muscles. This muscle coat acts as one of the thermoregulatory mechanisms that help in keeping each testis at a constant temperature.
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Fig. 1.2: Male genital organs
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Fig. 1.3: Spermatogenesis
Both fear and cold cause these muscles to contract in an action known as cremasteric reflex. Contraction elevates the testes to a position closer to the inguinal canal and thus closer to the body heat.
The temperature of the testes is lower then body temperature because of pampiniform plexus of veins, which surrounds the testes. Testes are the main production house for spermatozoa.
A total of about 72 days are needed for an immature spermatogonia to develop into a mature spermatozoa.
After the sperm are formed in the testes, they enter to the coiled tubule known as epididymis. Within this tubule, sperms are moved along by peristaltic action. Here they attain motility and their fertilization capability.
From the epididymis, sperm enter the vas deferens, through the inguinal canal and courses intraabdominally. The sperm and the accompanying fluids 6are then deposited in the prostatic urethra where the intra-abdominal portion of the vas ends after it has merged with the ducts from the seminal vesicle. After merging the vas deferens is known as ejaculatory duct.
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Fig. 1.4: Seminal vesicle
The seminal vesicle is a pouch like structure which contributes fructose (for the energy production of sperm) and other substances (used in the coagulation process) to the seminal fluid. Therefore, if semen does not coagulate, it can be assumed that the seminal vesicles are defective.
The prostate also contributes secretion to seminal fluid. Ejaculation occurs when the seminal fluid reaches the prostatic urethra and is propelled forward by the action of bulbocavernous muscle. Prior to the contribution of testes, the first fluid to be expelled from the 7penis is a lubricant secreted by the Cowper's gland followed by the prostatic fluid and then the bulk of sperms. The initial portion of the ejaculate contains highest numbers of sperms. The final fluid in the ejaculate comes from the seminal vesicles.
 
Hormonal Interaction in Female
The hypothalamus-pituitary-ovarian axis is the system which stimulates and regulates the production of the hormones needed for the normal sexual development and reproduction. Ovaries are under the direct influence of hypothalamus and pituitary glands through a complex system of positive and negative feedback. The hypothalamus produces luteinizing hormone-releasing hormone (LHRH). That, in turn, stimulates the pituitary gland to produce and release two gonadotropic hormones, follicular stimulating hormone (FSH) and luteinizing hormone (LH).
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Fig. 1.5: Hormonal interaction
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The action of this hormonal system is cyclical. Towards the end of menstrual cycle, production of oestrogen and progesterone by corpus luteum decreases. As a result, the negative feedback effect exerted by estrogen on the production of FSH is diminished and FSH levels begin to rise. When estrogen levels reach their lowest point, menstruation will occur. Simultaneously, with the menstruation, FSH and LH levels will rise gradually. The increasing quantities of gonadotropins will stimulate the growth of numerous ovarian follicles, which in turn, will produce ever-increasing levels of estrogen in response to the rising levels of LH and FSH. Out of many follicles that begin to mature, only one follicle will progress to become a mature graafian follicle. The others will degenerate and eventually become atretic. The dominant follicle produces more estrogen. As the cycle progresses, estrogen production increases and gonadotropins, primarily FSH, become somewhat depressed as a result of negative estrogen feedback. Eestrogen levels continues to rise and eventually exerts a biphasic feedback on hypothalamic-pituitary system that results in the burst of LH. This is called LH surge. Approximately 24 hours later, an ovum is extruded from the mature dominant follicle.
Following the ovulation, the dominant follicle becomes the corpus luteum, which begins to secrete progesterone and contributes to the production of estrogen. The augmented levels of these two hormones 9then sequentially transform the endometrial lining of the uterus into secretory lining in preparation for pregnancy. If pregnancy does not results (hCG is not secreted by the conceptus). The corpus luteum will stop releasing progesterone and hence, both, estrogen and progesterone production will begin to decrease and so menstruation will commence because of series of events. Simultaneously FSH levels have already started to rise in preparation of next dominant follicle.
 
Conception
Timing of coitus is very important for achieving pregnancy because of the short active life of both mature sperms and an ovum. Ovulation usually takes place on the 14th day of the 28 days of regular menstrual cycle. So 48 hours before and after this event chances of ovum to fertilize are maximized.
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Fig. 1.6: Seminal fluid at external OS
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Total ejaculation from the penis is primarily deposited at external OS of the cervix and posterior fornix of vagina. The total volume of the semen is about 2 to 6 ml. It is alkaline in nature with a pH of 7 to 7.5. Sperm concentration in a normal ejaculate ranges from 20 to 160 millions/ml.
The cervix acts as a ‘gate’ to the female reproductive tract. For the fertilization of the ovum to occur in the fallopian tube, the cervix must permit the sperms to pass through. This is facilitated by change in cervical mucus brought on by hormonal changes in the menstrual cycle. Preovulatory cervical mucus is thin, watery and acellular to help the sperm migration towards the uterine cavity. When the sperms enter the uterine cavity the presence of secretion from endometrium capacitate them to penetrate the zona pellucida the outer layer of ovum. Presence of fructose in the seminal fluid gives the sperm a source of energy to propagate. Seminal fluid is alkaline (pH 7 to 7.5). When it is mixed with the acidic vaginal fluid the pH becomes 6 or so. Sperms when enter the alkaline cervical canal they ascend rapidly towards uterine cavity. It is also because of the contractions of uterine muscles which are probably due to the presence of some prostaglandin present in the seminal fluid.
The two ovaries function as a one unit and between them, they normally shed only one ovum at a time. The ovaries have two functions (1) Production of ovum and (2) production of hormones. Under the hormonal influence one of the developing follicles in the ovary becomes dominant follicle.
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Fig. 1.7: Ovulation
The follicular fluid is increased in amount. The fully matured follicle, just prior to ovulation measures about 20 mm and is composed of theca externa, theca interna, membrana granulosa, granular cell layer, discus proligarous and antrum containing vesicle fluid.
Shortly, before the ovulation, the dominant follicle reaches the surface of the ovary. The follicular wall near the ovarian surface becomes thinner and then degenerates to release the ovum from the ovary. The word rupture of follicle implies an explosive or dramatic occurrence, but as a matter of fact the discharge of ovum from the follicle is a gradual process occupying many seconds. As the time of ovulation approaches, the outer end of fallopian tube moves towards the ovary so that the fimbria tends to embrace it and are ready to catch the ovum. This pickup function of the tube is vital for the further propagation of the ovum in the fallopian tube.
The time taken by the sperms to travel from the vagina to the fallopian tubes may be as short as one hour and varies from 6 to 24 hours.
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Fig. 1.8: Ovulation and ovum pickup
Soon after ovulation the ovum is picked up by the fimbria of the fallopian tube. In the ampullary region it is still enclosed by corona radiate. It is approached by numerous spermatozoa and few of which have function of softening the corona by releasing hyaluronidase. Ultimately one of the sperm penetrates the ovum and loses its tail and body. Sperm retains this property to enter the ovum for 24 to 48 hours. The ripe ovum can survive in fertilizable form for 24 hours. Conception should, therefore, take place within 24 hours after ovulation and hence the coitus must occur during this period.
When sperms meet the ovum pronucleus, it forms a single nucleus of 46 chromosomes. There after the fertilized ovum begins a series of cell divisions.
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Fig. 1.9: Fertilization
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The fertilized ovum is moved along the fallopian tube by the cilial current and by tubal peristalsis. In approximately 4 days it reaches to uterine cavity.
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Fig. 1.10: Embryo
The first division of the fertilized ovum into two cells occurs between 24 to 30 hours and after fertilization. That each cell divide again and again to form a morula. The nidation occurs in the prepared endometrium which nourishes the morula to develop into embryo.
If anything is wrong in the above mentioned list the end result is menstruation and failure to occur pregnancy.