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thesis on Fertility management in female of the subject REPRODUCTION BIOLOGY
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Uploaded on 01/25/2019
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Department of Zoology, Banaras Hindu University, Varanasi 221 005, India
Introduction:-
Reproductive Capacity or Fertility:-
Control of Fertility:-
Sterilization
Medical Termination of Pregnancy
Contraception
Infertilty
Conclusion
Table 1 To 3
Fertility is ability to reproduce or the physiological capacity to produce children. The explosion of information on hormonal regulation of reproductive processes in human have been applied to development of methods for ovulatory induction, avoidance of conception, treatment of infertility, increasing production of farm animals and promoting fertility of rare species. The fertility in female may be controlled artificially by three ways: (a) Sterilization; (b) Medical termination of pregnancy; and (c) Contraception. Female sterilization provides permanent method of birth control. It is a safe and simple surgical procedure. Medical termination of pregnancy is a legitimate choice for couples or women with certain conditions (such as rape, mental or physical stress or disorder) or with abnormal findings (such as a malformed or genetically diseased fetus or a placental tumor). Hormonal methods of contraception inhibit ovulation and bring about other changes in a women’s reproductive system. After 30 years of use, the pill is one of the best understood methods of contraception and for nearly all women the benefits of its use outweigh the risks by a wide margin. Continued research is needed for development of newer and safe methods for control of human contraception. Infertility is the state of a diminished capacity to conceive and bear offspring. Infertility is not an irreversible state. In females, the reproductive abnormalities that are commonly found include ovulatory disorders, tubal defects, endometriosis, and unexplained infertility. Assisted reproduction through in vitro fertilization offers the highest fecundability across a wide spectrum of reproductive tract disease.
or from defects in the genital tract, or, the absence of internal genitalia. However, even in normal females, early menstrual cycles are rarely regular. Some cycles are anovulatory, and may lack, or have short luteal phases. In general, the follicular phase tends to become shorter with age and the luteal phase tends to lengthen, for reasons that are unclear. Hormone production and reproductive tract morphology change with age, as does the fertility level.
Fertility is highest in women in their twenties and declines thereafter. This decline could be due to a reduction in fecundity or changes in sexual behaviour. The abilities to sustain a pregnancy through to successful parturition declines slowly to age 35 years and more rapidly thereafter when an increasing frequency of failed ovulation, perinatal or neonatal mortality, low birth weights, maternal hypertension, and congenital malformations are encountered. Accordingly, it is not surprising that irregular menstrual cycles may begin to reappear in some women in their early forties and mark the onset of the climacteric, a period of reproductive change that may last for up to 10 years before the last menstrual cycle (the menopause). This secondary amenorrhea occurs at a mean age of 52 years in the USA. Symptoms associated with the climacteric onset can include mood changes, irritability, loss of libido and hot flushes. The final cessation of reproductive life is the menopause. However, premature loss of oocytes, and premature menopause, occurs in about 2% of women, in some as early as their late teens and early twenties.
In most cases, natural mating results in optimum fertility. When sperm are collected, cooled, stored, extended in selected media, frozen or in other ways handled, the fertility is usually less than when large numbers of sperm are deposited naturally. Extending the semen almost universally means the concentration of sperm is also reduced. Fertility of semen declines with storage period. The chemical makeup of the extender can influence the effectiveness of the extender; thus, there is an ongoing search for combinations of components that will best preserve the fertilizing ability of stored sperm. Sperm of bulls are now most often stored in a frozen state and there is a continuous attempt to device procedures that will preserve fertilizing ability of sperm of many species both domestic and wild. Removing embryos from the mother and transferring them, freezing and storing them, and otherwise manipulating them reduce their chances of survival. Gamete and embryo manipulation can be a solution to an otherwise infertile condition. Sperm can be recovered from the male, oocytes can be recovered from the female, and fertilization can occur outside the body, and the embryo can be transferred back into uterus of a female and fertility is restored. Assisted reproductive technology (ART) has made it possible for infertile couples to produce young under a wide variety of conditions.
CONTROL OF FERTILITY:-
The socially accepted artificial controls over fertility available to varying extents in different societies are sterilization , medical termination of pregnancy and contraception. Not all of these methods are 100% effective and, thus, they should be seen as interventions for delaying births or increasing the interval between births.
A. STERILIZATION
Female sterilization provides permanent method of birth control for couples who have completed their families or wish to have no children. It is a safe and simple surgical procedure. It can usually be done with just local anesthesia and light sedation. Female sterilization is also known as voluntary surgical contraception, tubal ligation, tying the tubes, minilap, and the operation. In women, sterilization involves ligation, blocking of the fallopian tube (electrocoagulation) or removal of both end of fallopian tubes (salpingectomy) or a section of the oviduct (fimbriectomy). A general anesthesia is usually required, although
regional anesthesia can be used. The two common approaches are non-laparoscopies and laparoscopies.
Non-laparoscopic method:-
The tubes may be approached by conventional laparotomy, minilaparotomy, and colpotomy (an incision made tranvaginally at the top of the vagina between the cervix of the uterus and the rectosigmoid colon). Gynecologists are reluctant to perform a conventional laparotomy solely for tubal ligation except during another gynecologic or surgical procedure. In the immediate post partum period, the uterus is enlarged up to the level of the umbilicus requiring only 1 or 2 cm incision, which heals quickly leaving only a small scar. Several non- laparoscopic methods are used from time to time. Irving in 1924 described a method used exclusively for sterilization. Sterilization failure has not been described but the heavy bleeding may occur during the procedure. It is seldom used now. Pomeroy techniques are the other most widely used method for cesarean section patients or immediate postpartum sterilization. Kroener technique is also called a fimbriectomy, the removal of the end of the fallopian tube. This technique was meant to be used during colpotomy. The serious nature of complications encountered after vaginal tubal sterilization prohibit this procedure as a quick and effective means of performing female sterilization. Though, Uchida technique from Japan claims a zero failure rate.
Laparoscopic method:-
Anderson performed the first laparoscopic tubal occlusion in 1947, but this method became most popular in 1969. Laparoscopy offers the following advantages over non-laparoscopic techniques: 1. Small incisions whose scars are barely visible; 2. Same day surgery; 3. No vaginal drainage; 4. No sexual restriction; and Lower cost, etc. The disadvantages of laparoscopic sterilization are few. When compared to non-laparoscopic techniques, laparoscopy requires more training. It is more expensive.
How effective is Sterilization?
It is very effective and permanent. In the first year after the sterilization, failure rate was 0. pregnancies per 100 women (fails in 1 in every 200 women undergoing sterilization). Within 10 years after the sterilization, it comes about 1.8 pregnancies per 100 women. Postpartum tubal ligation is one of the most effective female sterilization techniques.
Advantages of Sterilization:
Disadvantages of Sterilization:
The latter approach is particularly useful in the first month of conception. The failure rate using these approaches is low (1-1.5%) and complications, such as major blood loss, incomplete aspiration or damage to the cervix or uterus, are about 2-3%. The side effects of post operative infection and damage to the uterus or cervix may affect subsequent fertility.
The possibility of conducting totally medical out-patient abortions without the need for surgery under aseptic conditions has been realized with the development of orally active anti- progestins (such as mifepristone or RU 486), which compete for progesterone receptors. They are more than 98% effective if combined with a low dose of orally active prostaglandin (misoprostol) given 36-48 hours later. Treatments are usually given within 7 weeks after the onset of the last menses. However, side effects include nausea, vomiting and abdominal pain.
C. CONTRACEPTION
Contraception is defined as the temporary prevention of fertility. Contraceptives are devices that diminish the likelihood of conception. All contraceptive methods have a failure rate. Each of the various methods of contraception currently available has certain advantages and disadvantages. Therefore, when giving advice about contraception, the clinician should explain to the couple the advantages and disadvantages of each method so that they will be truly informed and can rationally choose the method most suitable to them.
Among all reversible method of contraception, Oral Contraceptives (OC’s) or Birth control pills (also known as "the Pill"), are most popular and are used by about 26% of all women in USA. Intra-uterine device (IUD) and progestin implants are two other most effective devices. Other commonly used contraceptive methods are condom, withdrawal, periodic absentinence, diaphragm, and spermicides. IUDs have low failure rates but occasionally cause serious side affects. Vaginal barriers have moderate failure rates and have no systemic effects, although they can be responsible for temporary and local problems. Some vaginal barriers offer protection against sexually transmitted diseases and HIV infection. Details of commonly used contraceptive methods are described under following head:
The Natural method is based on the strategy of avoiding unprotected vaginal intercourse during the unsafe or fertile time of the menstrual cycle. The unsafe or fertile times are the days of the menstrual cycle when woman can become pregnant. Ovulation occurs at approximately mid-cycle. The potential life of spermatozoa in the female genital tract ranges 3 to 4 days and ova or egg survives for about 12 to 24 hours. A woman can use this information together with following ways to determine her unsafe or fertile time: a. Calendar or rhythm method; b. Cervical secretion; c. Basal body temperature.
a. Calendar or Rhythm Method: A woman can count calendar days to identify the start and end of the fertile time. Before relying on this method, the woman records the number of days in each menstrual cycle for at least 6 months. The first day of menstrual bleeding is always counted as day 1. The woman subtracts 18 from the length of her shortest recorded cycle. This tells her the estimated first day of her fertile time. Then, subtract 11 days from the length of her longest recorded cycle. This tells her the last day of her fertile time. The couple may avoid conception, using a barrier or withdrawal method during the fertile time.
Example: If her recorded cycles vary from 26 to 32 days: 26-18=8; 32-11=21. So, between day 8th^ to 21 st^ of the menstrual cycle are unsafe or the fertile period. The woman can have unprotected sex before day 8 and after day 21 of the menstrual cycle.
b. Cervical secretion: A woman checks her cervical secretion everyday. She may feel wetness at the opening of her vagina or see secretions on her finger, underpants or tissue paper. The secretions have a peak day, when they are most slippery, stretchy, and wet. When a woman sees or feels cervical secretions, she may be fertile. The couple should avoid sex or use protected sex until the 4th^ day after the peak day.
c. Basal body temperature: A woman’s resting body temperature goes up slightly around the time of ovulation (release of an egg), when she could become pregnant. The woman must take her body’s temperature in the same way at the same time each morning before gets out of bed. The woman’s temperature rises 0.2 0 to 0.5^0 c (0.4^0 to 1.0^0 F) around the time of ovulation.
Woman should identify unsafe or fertile and safe or infertile days by combining basal body temperature and cervical secretion observations together with calendar or rhythm method and often, other signs and symptoms of ovulation.
How effective is Natural method?
Natural methods are effective or very effective, when used consistently and correctly. When single – indicator method is used consistently- 3 pregnancies per 100 woman in first year of use occurs in cervical secretion, 1 pregnancies per 100 woman in first year of use in basal body temperature and 9 pregnancies per woman in first year in calendar method. All the three method together showed 2 pregnancies per 100 women per year.
Advantages:
1.Once learned, can be used to avoid pregnancy or to become pregnant, according to the couple’s wishes. 2.No physical side effects. 3.Very little or no cost. 4.Effective if used correctly and consistently. 5.Immediately reversible. 6.No effect on breastfeeding or breast milk. No hormonal side effects. 7.Involves men in family planning. 8.Educates people about woman’s fertility cycles.
Disadvantages:
Advantages : It is safe method that almost every woman can use. It has following advantages: Help to prevent some STDs and conditions caused by STDs; May offer some protection against HIV/AIDS; No daily action needed; It offers contraception just when needed; No hormonal side effects; Can be stopped at any time; Easy to use with little practice; May increase vaginal lubrication; and Can be used immediately after childbirth.
Disadvantages : Spermicides may cause irritation to woman or her partner, especially if used several times a day. It may cause local allergic reaction and can make urinary tract infections more common. Interrupt sex if not inserted beforehand.
3. Hormonal Contraception:
Hormonal method of contraception inhibits ovulation and brings about other changes in a woman’s reproductive system that prevents pregnancy. The introduction of the pill revolutionized family planning because use of the pill does not interfere with sexual intercourse. Some of the effects of pills are unrelated to contraception; some are harmful, such as changes in the cardiovascular system, whereas others are beneficial, such as marked reduction in the incidence of some important female concerns. After 30 years of use, the pill is one of the best studied drugs and for nearly most women the benefits of use outweigh the risks by a wide margin.
Hormonal contraceptives can be divided into: i. Oral Contraceptives; ii Implants, iii. Injectable Contraceptives; and iv. Emergency Contraceptives.
i. Oral Contraceptives :
Oral contraceptives (OCs) are commonly of two types: (a). Combined OCs; and (b). Progesterone only pills (Mini pill)
a. Combined Oral Contraceptives (COCs):
The combination formulations are the most widely used and most effective. They consist of tablets containing both an Estrogen (E 2 ) and progesterone (P 4 ) given continuously for 3 weeks (20 days). The treatment is stopped for 1 week (5-7 days). The OC’s promotes breakthrough bleeding. Withdrawal bleeding usually occurs in the week when no steroid is ingested. It lasts 3 to 4 days and uterine blood loss is relatively less than during menses in normal ovulatory cycle. COC’s with more than 50 μg of E 2 were associated with greater incidence of adverse effects without greater efficacy; they are no longer marketed for contraceptive use in the USA, Canada, and UK. The present day COCs contain very low doses (about 20-30 ug of Estradiol) of hormone. They are called low dose COCs (second generation pill).
All currently marketed formulations are made from synthetic steroids and contain no natural estrogens or progestins ( Table 1 ). There are two major types of synthetic progestins: 19- nortestosterone derivatives and 17 α-acetoxyprogesterone derivatives. Medroxyprogesterone acetate and megestrol acetate are C 21 progestins. The 19-nortestosterone progestins used in OC’s are of two major types, called estranes and gonanes. The various estranqes used in OCs are norethynodrel, norethindrone acetate and ethynodiol diacetate. The parent compound of the gonanes is dl-norgestrel, which consists of two isomers, dextro and levo. The levo form is biologically active. The progestins are combined with varying dosages of two estrogens, ethinyl estradiol and ethinyl estradiol 3-methyl ether, also known as mestranol (Fig. 1).
Table 1: Composition of several commercially available oral contraceptives
Trade name Progestogen Estrogen Enovid Norethynodrel Mestranol Norinyl, orthonovum Norethindrone Mestranol Metrulin,ovulen Ethynodiol diacetate Mestranol Lormin Chlormadinone Mestranol Delpregnin Megestrol acetate Mestranol Provest, farlutal Medroxyprogesterone acetate
Ethinyl estradiol
Norlestrin Norethindrone acetate Ethinyl estradiol
Mode of action of COCs: It prevents conception by several mechanisms.
The primary effect: The COCs prevent ovulation by inhibiting gonadotrophin surge (negative feedback) via an effect on both pituitary and hypothalamic centers.
3. Not highly effective unless taken every day. Difficult for some women to remember everyday. 4. New packets of pills must be at hand every 28 days. 5. Not recommended for breast feeding women because they affect quality and quantity of milk. 6. Blood clots in deep veins of the legs or heart attack. Those at higher risk are women with high BP and women who are age 35 or older and at the same time smoke more than 20 cigarettes per day. 7. Do not protect against sexually transmitted diseases (STDs) including AIDS. 8. Body weight: Some women gain weight, but the majority show no change. The increase has a variety of different causes. In some cases it is a simple result of increased appetite and food intake. Other women may show mild fluid retention, due to the estrogenic component. Finally, there is evidence that some COCs have an anabolic effect, so that muscle mass increases.
Effectiveness of COCs:
Administration of small dose (500 ug) of progesterone to women results in pregnancy failure. Thus, the mini pill was designed containing a small dose of a progestational agent and must be taken daily in a continuous fashion (day 5-25). Mini pill contained one half to one third as much progestin as combined OCs. They do not contain estrogen. The mini-pills are also called as progestin-only pills. The dose level of progesterone appears to be fairly critical. It must be sufficiently high to have an adequate antifertility effect but low enough to avoid a high incidence of irregular bleeding ( Table 2 ).
Table 2: Composition of commercially available mini pills (Progesterone only pills)
S.No. Trade Name Name and dose of hormone
Mechanism of action:
Progesterone only pills have complex effect that relates to the dosage of progesterone. Its major actions are:
Effectiveness:
Advantages and Disadvantages of Mini Pill or Progestin Only:
Advantages:
levonorgestrel 25μg/day. Norplants are placed subcutaneously in a fan like manner in the upper arm.
Effectiveness:
Norplants is highly effective, with low pregnancy rates 0.7 per 100 women at 4 years of use. Pregnanacy rate 0.01/100 in the first year of use.
Mode of action: The various mechanisms by which Norplant affect fertility are described below:
Disadvantages:
any of these side effects and most side effects go away without treatment within the first year.
The most common type of injectable contraceptives are: 1. DMPA: Depot- medroxyprogesterone acetate or Depot-provera. Use dose of 150 mg given every 3 months and 2. NETEN: Also called Noristerat (Norethisterone enanthate). It is in the dose of 200 mg given every 8 to 10 weeks. Monthly injectable contraceptives are also available. These includes: 1. Cyclofem : Oestradiol valerate 5 mg plus medroxyprogegterone acetate 25 mg; and 2. Merigyna: Oestardiol cypionate 5mg plus norethisterone enanthate 25 mg.
How effective:
Very effective- 0.3 pregnancies per 100 women in the first year of use (1 in every 333).
Mode of action: The various mechanisms by which injectable contraceptives affect fertility are described below:
Advantages:
Copper-bearing IUDs (made of plastic with copper sleeves and/or copper wire on the plastic). TCu-380 and MLCu-375 are this type.
Less widely available are: (a). Hormone-releasing IUDs (made of plastic; steadily release small amounts of the hormone progesterone or another progestin such as levonorgestrel). LNG-20 and progestasert are this type. (b). Inert, or unmedicated IUDs (made of plastic or stainless steel only). Lippes Loop was this type- all plastic.
How does it Work?
The biological action of IUDs, like that of pill, probably depends on interrupting a number of processes essential for conception. IUDs work chiefly by preventing sperm and egg from meeting. The device greatly reduces the number of sperm reaching the fallopian tubes, where the egg is fertilized. If fertilization takes place, an IUD may also act by preventing implantation.
How Effective?
TCu-380A IUD (widely available and lasts at least 10 years): Very effective as commonly used- 0.8 pregnancies per 100 women in first year of use (1 in every 125). Slightly more effective when used correctly-0.6 pregnancies per 100 women in the first year of use (1 in every170). Rates for the MLCu-375 (which lasts 5 years) are nearly as low. Various other copper-bearing and inert IUDs: Effective as commonly used- 3 pregnancies per 100 women in first year of use (about 1 in every 30).
Advantages:
