Pharma Tips

Contraceptive Methods

By: Mitul Shah | Views: 7818 | Date: 29-Jun-2010

Through the centuries, women and men have been searching for the ultimate contraceptive. Many different methods have been tried and many have failed. Some have been painful or comfortable and others ineffective and others effective. Either way different methods have been past down from generation.

Contraceptive Methods

Contraceptive Methods


HISTORY
Through the centuries, women and men have been searching for the ultimate contraceptive. Many different methods have been tried and many have failed. Some have been painful or comfortable and others ineffective and others effective. Either way different methods have been past down from generation. In the paragraphs below histories of various methods of contraceptives will be discussed.
The first method is the natural method. In the past, women used to nurse their children for two or three years. This would suppress ovulation protecting them from pregnancy. Another natural method is coitus reservatus or withholding ejaculation. This meant that the male would not ejaculate in the female, but hold the ejaculation back. Another effective natural method is coitus interruptus or withdrawing before ejaculation. The process of coitus interruptus involves the male withdrawing the penis from the female before ejaculation occurs. Most of these methods were effective yet dangerous.
 
 The rhythm method is basically abstaining from intercourse during ovulation. The Greek gynecologist Soranus, in the second century AD, was correct when he said that women were fertile during ovulation, but wrong when he said that ovulation occurred during menstruation. Researchers were not able to determine which days were safe until 1930. Because of the lack of knowledge in the area of contraceptives, most women had to rely on various potions and rituals.
Olive oil, pomegranate pulp, ginger, tobacco juice were frequently smeared on or around the vagina. Many times the only effect these contraceptives had was that they killed or slowed the sperm down before reaching the egg. Still other women used mixtures of crocodile dung along with honey or gums from various trees. They would insert these mixtures prior to intercourse.
The history of oral contraceptives is as bizarre as the mixtures. Many oral contraceptives were drinks containing oils, fruits, grains, and other vegetable matter. Soranus suggested drinking the water that the blacksmiths used to cool hot metals. Other oral contraceptives included urine and animal parts along with mercury, arsenic, or strychnine.
Certain methods involved a jerking motion with the intent of rerouting or dislodging the sperm. Soranus suggested that Greek women jump backward seven times after intercourse. Women of Europe were encouraged to turn the wheel of a grain mill backwards four times at midnight.
Douches also were used as birth control. French prostitutes had been using syringes to douche since 1600. This was seldom an effect method of contraceptive unless the douche was acidic.
In the past, barriers were the most effective. A barrier prevents the sperm from getting to the egg. Sea sponges made of soft wool were soaked in vinegar or lemon juice to create a spermicide. Sometimes half of a lemon was stuck in the vagina. Still other times a large wooden block was placed in the vagina but this was uncomfortable and deemed a device of torture. Oriental women used oiled paper "capping the cervix" was effective while European women used beeswax.
Historians attribute the intrauterine devices (IUDs) to the Arabs. They would stick pebbles into the uteruses of their camels to prevent them from getting pregnant on long trips across the desert or to market. What the IUD does is create a mild infection in the uterus that prevents the fertilization and implantation of eggs.
Before the IUDs were the pessaries that were placed in vagina with a portion penetrating the cervix to enter the uterus. German gynecologist Grafenberg developed one from gut and silver wire in 1920. In 1965, women wore polyethylene pessaries but the woman had to be pregnant once before she could wear one. Then in the 1970s, copper pessaries were popular because any women could wear one.
The females are not the only ones with a form of contraceptive. The male can use a condom, a small covering used to cover the penis and catch the sperm as it ejaculates. In folklore, "Dr. Condom" invented a condom for King Charles II in the 17th century, but in reality there was not any "Dr. Condom." In actuality, Egyptians wore condoms made out of fabric not as a contraceptive but as protection from insect bites. A man named Charles Goodyear developed the first rubber condom in the 19th century. In the early 1990s, a condom for women was invented. But instead of fitting a penis it fits inside the female.
The most recent addition to the list of contraceptives is female sterilization, which through the process of surgery the Fallopian tubes are blocked or cut. The women still ovulate but the egg never makes it through the Fallopian tubes. It is the most widely used method of contraception today. [1]

INTRODUCTION
Introduction to Contraception
The Society of Obstetricians and Gynecologists of Canada (SOGC) recognizes family planning as an important aspect of life and a basic human right.Yet there are many barriers to accessing an appropriate method of contraception and using it consistently and correctly, particularly for individuals with low incomes and low levels of literacy.One study found that 8 of 14 condom package inserts required a level of literacy consistent with high school completion.Another study found that 75% of patients needed help in understanding the package inserts in oral contraceptives.
What's so different about research on contraceptives? They're just like other drugs or devices. Aren't they?
Contraceptives `re not just "drugs" hey do not treat a state of 'illness' They are taken by people who may otherwise be healthy- though the user's state of health is a major consideration both in research and otherwise.
Contraceptives are used because most people, especially women, need them badly enough to interfere with their normal bodily processes - a need which would force many people to accept whatever is available.
Contraceptives are used over a long period of time on a continuous basis. Any interference with the body's normal functioning will occur for an extended period - something to be remembered when determining the safety and harmlessness of a method.
Contraceptives obviously affect the reproductive cycle, and could possibly affect the next generation. Most important , contraceptives satisfy a social , not medical need.
Contraceptive research should be seen in the context of the growing "technologising" of health care, the medicalising of disease diagnosis and treatment, an increasingly market-governed process, controlled by the pharmaceutical industry.
Contraceptive research gets justification from the population control lobby. This lobby directs the research, its language dominates in both the popular press and research setting, and it justifies the introduction of potentially risky methods. The other, more sophisticated justification for introducing potentially risky contraceptives is that they reduce maternal mortality by preventing pregnancy itself.
However, 'population control' actually means control of certain populations. By now we know it to be racist and anti-poor. Its implementation is also associated with anti-semen attitudes. Women are considered for reproduction, as they are for exercising control over this process. Contraceptive research follows the same line of thinking, even if it is at the cost of women's health.

Contraception allows you to choose when and if you want to have a baby. Some forms of contraception also provide protection against sexually transmitted infections (STIs).
There are several types of contraception, which work in different ways. Barrier methods, such as male and female condoms, create a physical barrier against sperm. Women can also use hormonal methods of contraception, such as the pill, or mechanical contraceptive devices, such as an IUD (intrauterine device) that is placed in the womb.
Before recommending a contraceptive, your GP will assess your age, medical history, and sexual lifestyle. No contraceptive is 100% reliable, and some have possible side effects. It is therefore important to consider these factors when deciding what sort of protection to use.
Condoms are available for free from your family planning clinic, sexual health clinic, or lxtt       GUM (genitourinary medicine) clinic. They may also be available from your GP. Emergency contraception is also available from your GP, family planning clinics, most NHS walk-in centres (England only) and some pharmacies. You can buy male and female condoms from chemists, as well as from vending machines, supermarkets, garages and other shops.
You may need to change your contraception as you get older, after having children, or if your sexual lifestyle changes. It is worth remembering that the male condom is the only form of contraception that also protects you from sexually transmitted diseases. In all cases, contraceptive methods are more reliable if used properly.

DIFFERENT TYPES OF CONTRACEPTIVE METHODS

Contraceptive methods are, by definition, preventive methods to help women avoid unwanted pregnancies. they include all temporary and permanent measures to prevent pregnancies resulting from coitus. The last few years have witnessed a contraceptive revolution, that is, man trying to interfere with the ovulation cycle.
The various methods are:

[A]SPACING METHODS:


1.BARRIER METHODS

(a)Physical methods
(b)Chemical methods
(c)Combined methods

2.INTRA-UTERINE DEVICES
3.HORMONAL METHODS
4.POST CONCEPTIONAL METHODS


[B]TERMINAL METHODS

1.MALE STERILIZATION
2.FEMALE STERILIZATION


BARRIER METHODS
The aim of these methods is preventing the live sperm from meeting the ovum. These methods require a high degree of motivation from the part of the user.  They are less effective than pill or loop. [3]They are only effective if they are used consistently and carefully.

Physical methods

1.CONDOM
Condom is the most widely used barrier  device by the males around the world. In India it is better known by its trade name NIRODH, a Sanskrit word, meaning prevention. . Condom is receiving new attention today as an effective, simple “spacing” method of contraception, without side effects. In addition to preventing pregnancy, condom protects both men and women from sexually transmitted diseases.
Condoms are manufactured in India by HINDUSTAN LATEX in Trivandrum, and London rubber industries in madras. It has been estimated that 72 condoms per year may be needed to protect a couple.
Surveys have reported pregnancy rates varying from 2-3 per 100 women-years to more than 20 on using condoms. [7]
Also 72 condoms per year may be required to protect a couple. [8]
 
2. DIAPHRAGM
The diaphragm is a vaginal barrier. It was invented by a german physician in 1882. also known as ‘Dutch cap’ , the diaphragm is a shallow cup made of synthetic rubber or plastic material. It ranges in diameter from 5-10 cm. It has a flexible rim made of spring or metal .It is important that a woman be fitted with a diaphragm of the proper size which is determined by inser two fingers into the posterior fornix and noting how far on the finger the symphysis pubis comes. This distance indicates the approximate diameter of the diaphragm needed. [6] In the correct position , it lie snugly between  the symphsis pubis and the sacrum. It is held in the position partly by the spring tension and partly y the vaginal muscle tone. This means, for successful use, the vaginal tone must be reasonable. Otherwise in the case of a severe degree of cyctocele, the rim may slip down. A spermicidal jelly is always used along with it. [9]
Variations of the diaphragm include the cervical cap, vault cap and vimule cap. These devices ae not recommended in the National Family Planning Programme. [10]

 

3. VAGINAL SPONGE

Another barrier device employed for hundreds of years is the sponge in vinegar or olive oil, but it is only recently one has been commercially marketed in USA under the trade name TODAY for the sole purpose of preventing contraception. It is a small polyurethane foam sponge measuring 5cm by 2.5cm, saturated with the spermicide, nonoxynol-9. The sponge is far less effective than the diaphragm, but it is better than nothing. [11]

 

b. CHEMICAL METHODS

In the 1960s, before the advent of iuds and oral contraceptives, spermicides were widely used. They comprise four categories [12]

Foams: foam tablets, foam aerosols.
Creams, jellies and pastes-squeezed from a tube.
Suppositories-inserted manually
Soluble films-C.film inserted manually.

The spermicides contain a base into which a spermicide is incorporated.
Commonly  used  modern spermicides are “surface active agents” which attach themselves to spermatozoa and inhibit oxygen uptake and kill sperms. [13]

INTRA UTERINE DEVICES

IUDs are obtained only by prescription and must be introduced correctly by a health care professional. A pelvic exam is essential for an IUD insertion. The IUDs can be inserted into the uterus at any time when you are not pregnant. [14]
You may have limited side effects with IUD such as cramps, spotting, heavy menstrual flow, infection, and infertility. Complications occur in rare case such as perforation, heavy bleeding, abnormal spotting, and smelly discharge. You should see the doctor immediately if any of these symptoms occur.
Also, you need to check your IUD in the uterus every month because the uterus sometimes expels the IUD. It is also important to check the birth control device (IUD) periodically by your doctor.

What is an IUD?

The letters "IUD" stand for "intrauterine device." IUDs are small, "T-shaped" contraceptive devices made of flexible plastic and are surgically implanted into a women's uterus. Intrauterine Device (IUD) is a kind of birth control method used by women. The IUD is a “T” shaped device made-up of molded polyethylene plastic coated with barium, which can be seen on X-ray.
Generally it is placed into the uterus where the base of the T will be placed over the cervix and the arms extend horizontally across the uterus. When the device is placed into the uterus, the arms of the “T” are folded down but they then open out to form the top of the “T”.
There will be a short plastic string attached to the IUD, which will extend through the cervix into the vagina. This string ensures that the IUD (birth control device) is still in the uterus.

There are two IUDs available on the US market, the Progestasert and the Paragard copper-T. The IUD remains a medically safe method for many women and is the reversible contraceptive method used by more women across the globe.

How does it work to prevent pregnancy?

IUDs work by preventing an egg from being fertilized, although scientists are not exactly sure how this happens. Theories about this process include:
It affects the way the sperm or egg moves
Substances released by the IUD immobilize sperm
It moves the egg through the fallopian tube too fast to be fertilized.
The copper in the ParaGard adds to the effectiveness of the IUD in other ways. It affects the lining of the uterus by not allowing an egg to implant and it stimulates the production of prostaglandins, chemicals that affect the hormones needed to support a pregnancy. The ParaGard can be a long-term method that may be left in for 8 years.
The birth control method of s (IUDs) is of two types: Intrauterine contraceptive device (IUCD) and Intrauterine system (IUS).
IUCD is made of copper and releases copper from a copper wire that is wrapped around the base where as IUS releases the hormone progesterone from the vertical part of the ‘T’.
Still, it is unknown about how IUDs work. However, they prevent birth control by causing a localized inflammation that starts about 24 hours after insertion.
This leads to an inflammatory reaction in the uterus that draws white blood cells, which produce substances that are toxic to sperm. The IUDs that release progesterone cause a slight change in the endometrial environment that harms the implantation of the egg in the uterine wall. It also changes the cervical mucus, which, in turn, controls the sperm from getting into the cervix.

The Progestasert IUD prevents pregnancy by releasing the hormone progestin, which thickens the cervical mucus. This acts as a barrier to prevent sperm from entering the uterus. The Progestasert also affects the lining of the uterus to prevent an egg from being implanted. Because of the hormonal component of the Progestasert, it must be replaced yearly.

Who should not use an IUD?

There are many reasons why you might not want to choose an IUD as a method of contraception. The IUD is not recommended in the following circumstances:
Active pelvic infection or a history of pelvic inflammatory disease (PID)
Known or suspected pregnancy
Multiple sexual partners
Cervicitis (inflamed or infected cervix)
Bleeding disorders
History of ectopic pregnancy (pregnancy developed in fallopian tubes)
Impaired response to infection (AIDS, diabetes, steroid treatment, etc.)
Severe cramping with periods
Heavy menstrual flow
Allergy to copper
Anemia
History of a sexually transmitted infection
Previous pelvic surgery
Plan to have children in the future
Who have more number of sexual partners[23]
Types of IUDs

Medicated IUDs have either copper or hormones added to a plastic frame.

The first generation of copper IUDs, which included the Cu-7, the TCu-200, and the Multiload-250 (MLCu-250), carried copper wire with a surface area of 200 to 250 mm2.


The second generation of copper IUDs introduced several innovations—more copper wire, copper sleeves, and/or a silver core to the copper wire (denoted by Ag in the IUD name). These changes increase effectiveness and extend effective lifespan . The major second-generation IUDs are the TCu-380A, TCu-220C, Nova T, and Multiload-375 (MLCu-375).
Hormone-releasing IUDs constantly release small amounts of steroid hormone into the uterus. The Progestasert, which has been marketed since 1976, contains 38 mg of progesterone released at a rate of 65 micrograms per day for one year. The LNG-20 IUD contains 52 mg of levonorgestrel released at a rate of 20 micrograms per day and lasts at least five years. Since the early 1990s it has been approved for use in Denmark, Finland, Norway, and Sweden. Recently, the LNG-20 has also been approved in Belgium, France, Iceland, Singapore, Switzerland, and the United Kingdom.
The Lippes Loop[16] , made of polyethylene, was the most widely used unmedicated IUD outside China. This IUD is no longer distributed internationally. The other major types of unmedicated IUDs are flexible stainless steel rings (either round or in the shape of the uterine cavity and made with a single or double coil). These rings have been widely used in China but not elsewhere.
Researchers continue to develop and test new IUDs that may reduce expulsion rates and side effects. Among the devices being considered are a smaller, lightweight, and flexible T-shaped copper IUD, the Cu-SAFE 300, which can be inserted without a plunger and is designed to move towards the uterine fundus (the top of the uterus) when the uterus contracts. A frameless IUD consisting of six copper sleeves on a surgical nylon thread is called the FlexiGard 330, GyneFix™, or CuFix PP330. The thread is knotted at one end, which is anchored in the muscle of the fundus. [17] In clinical trials the device has proved to be highly effective and comfortable to use. Researchers in Switzerland have taken yet another approach: a copper-bearing IUD with a T-shaped frame, called the Sof-T. The tip of each end of the arm consists of a soft ball, designed to prevent perforation and to block the openings to the fallopian tubes in order to prevent sperm from entering. [18]

 

HORMONAL  CONTRACEPTIVES
Gonadal steroids
Exert Facilitating and ``Buffering'' Effects on Glucocorticoid-Mediated Transcriptional Regulation of Corticotropin-Releasing Hormone and Corticosteroid Receptor Genes in Rat Brain
Gonadal steroids profoundly influence several brain functions and are apparently responsible for gender-specific differences in the regulation of hypothalamic-pituitary-adrenal (HPA) secretions. In this study, we examined the so-called ``activational'' effects of gonadal steroids on the glucocorticoid-mediated regulation of the gene transcription of corticotropin-releasing hormone (CRH) and corticosteroid receptors in brain areas of relevance for the control of pituitary-adrenal secretion. The efficacy of adrenalectomy (ADX) and chronic treatment with high doses of corticosterone (B) to regulate the gene transcription of CRH and corticosteroid receptors in the hypothalamic paraventricular nucleus (PVN) and hippocampus was studied in male and female rats under the conditions of deprivation of gonadectomy (GDX) and replacement with different gonadal steroids, such as estradiol (E2), progesterone (P), and dihydrotestosterone (DHT). In both sexes, ADX alone or in combination with GDX increased, and B treatment suppressed, the steady-state levels of CRH and corticosteroid receptor mRNAs, whereas GDX alone failed to affect any of the parameters studied. Administration of gonadal hormones to steroid-deprived (ADX/GDX) animals partially attenuated the upregulation of mRNAs encoding corticosteroid receptors in the hippocampus. Supplementation with gonadal steroids modified the effects of B on the gene transcription of CRH and corticosteroid receptors. Whereas P alone or in combination with E2 counteracted the B-induced downregulation of GR and CRH gene transcription in females, DHT and E2 administration further potentiated the effects of B on these parameters in a sex-specific manner. Taken together, the results indicate that gonadal steroids have minor influence on MR, GR, and CRH gene transcription under basal conditions, exert ``glucocorticoid-like'' effects on the transcription of corticosteroid receptors in the hippocampus of steroid-deprived animals, and interact with glucocorticoid-mediated mechanisms of regulation in the HPA axis through gender-specific ``buffering'' and ``potentiating'' effects. [19]

 

New female barrier methods
Research has continued to develop several new female barrier methods that are modified versions of diaphragms, cervical caps, and sponges. These devices have been designed to be easier to insert and remove, and more difficult to dislodge during intercourse.
The Lea's Contraceptive™ is a modified diaphragm-like device in one size. It is available as an over-the-counter product in Germany, and was approved by the United States Food and Drug Administration (U.S. FDA) in March 2002. It should remain in place at least 8 hours after intercourse, but be worn no longer than 48 hours before removing to wash. A study carried out by CONRAD indicated that the 12-month pregnancy rate of the Lea Contraceptive™  compared favorably with other barrier methods. Pregnancy rates associated with the Lea Contraceptive were 15 percent, compared to the 10 to 21 percent for the standard diaphragm with spermicide.
The FemCap™ is a modified cervical cap with a strap to aid in removal of the device. It is available in some European countries and was approved for use in the United States in March 2003. In a study by CONRAD and Family Health International, the FemCap™ used with spermicide waS found t/ be somewhat less effective as a contraceptive than a contentional diaphragm with spermicide. CONAD e3timates a 12%month pregnancy rate (based on 6-lonth pregnancy rates) of about 23 percent for the FelCap™ (FHI 2000; CONRAD 2000). [20]

 

New implants
Norplant, introduced in the 1980s, was the first contraceptive implant that became available to family planning programs. Despite the changes in menstrual bleeding patterns common to all progestin-only methods, Norplant proved highly acceptable to many women. Progestin implants for female contraception are now growing into a family of nations. So far, four different progestins and two polymers have been used to design six different implants  [21]

Norplant
(Population Council)  A system of six Silastic capsules that release levonorgestel
Duration of action-8 5 years
Registered in 60 countries
Used by nearly 6 million woman
Jadelle
(Population Council)            Silastic rods that release, evnorgestrel
Duration of action is 2- 5 Years
Ongoing registration an Europe
Implajon
 NV Organ)  A Single implant system that releases etonogeq4rel
Duration of action: 3 years
Registered an Australia Indonesia, and 11 European countries
Introduced in the Netherlands and the united
kingdom in September 1999
UniPlant  A single-rod, one-year implant that delivers nomegesdro, acetate
No commercialization plans at this time 

New injectables
Two new, once-a-month, combined injectable contraceptives have been developed by the Special  Program of research in Human Reproduction (HRP) of the World Health Organization. Both Cyclofem (also called CycloProv%ra or Lunelle) and Mesigyna have been tested on large multicenter clinical trials, and have been proven effective with relatively low incidence of side affects. Recent studies on the efficacy, causes of discontinuation, and side effects of the these two injectable contraceptives in Egypt sound they could be a positive addition to contraceptive choice [22]
 
Microbicides
With almost 34 million people worldwide living with HIV/AIDS—95 percent of whom are in developing countries—the need for additional prevention options has become urgent. Globally, women represent 43 percent of people infected by HIV/AIDS; more than 55 percent of people infected in sub-Saharan Africa, 30 percent in Asia, and 20 percent in Europe and the United States (Population Council and International Family Health 2000). [24]
A microbicide—a compound that can be applied inside the vagina or rectum to protect against sexually transmitted infections—ultimately may be formulated as a gel, cream, film, or suppository. An ideal microbicide should be effective, safe, acceptable, affordable, colorless, odorless, stable, easy to store and use, available in a variety of preparations, available in contraceptive and noncontraceptive formulations, and available without a prescription. At this time, however, the top priorities are to develop a microbicide that would provide protection when used consistently, and to develop a microbicide that would be used by those who need it most [25]
It is important to support the development of microbicides because: (1) diagnosis and treatment of STIs continues to spread despite knowledge of successful HIV-prevention strategies; (2) microbicides offer an alternative to condoms as a feasible means of primary prevention; and (3) currently available HIV-prevention techniques may not be feasible for many women in resource-poor settings. In addition, microbicides are an option that women can use that may not require the cooperation of her partner. A recent cost-benefit analysis, conducted at the London School of Hygiene and Tropical Medicine, indicated that introducing a microbicide which reduces infection by 40 percent at 30 percent coverage could avert approximately six million HIV infections among men, women, and children in 73 lower-income countries.
 

Microbicide research
 Microbicide research falls into two general approaches: (1) developing and testing new substances, and (2) investigating the potential microbicidal activity of existing spermicidal products and different formulations of these products.
Although researchers are examining more than 50 substances as possible vaginal microbicides—and about a quarter of these are in various stages of testing with humans—this group of experimental products is years away from being widely available.
Quinacrine sterilization
Intrauterine application Of quinacrine hydrochloride is a method of nonsurgical female sterilization that has received considerable attention during the last decade and has generated significant controversy. To date, more than 100,000 women in over 2  countries have been sterilized using this method, mainly in Viet Nam, India, and Pakistan. Inserted directly into the uterus in Pellet form, quinacrine liquefies and flow3 into the fallopian tubes, causing permanentscarring. Although recorded failure rates and persistent side effects related to quinacrine sterilization have been low, controversy has developed around quinacrines long-term safety, efficacy, and link to upper genital tract infections. As a result, several countries and regulatory agencies( including the U.S. FDA, have taken steps to ban both the manufacture and use of quinacrine for sterilization Animal trials are currently underway to resolve the toxicological questions about quinacrine's safety.

Products being evaluated act in one or more of the following mechanisms.
 Mode of Action  Examples
 Detergent-like chemicals that disrupt the lipid membrane of the cell and the surface of HIV.
 Existing spermicides such as nonoxynol-9, octoxynol-9,  benzalkonium chloride, menfegol, and N-docasanol.

 Prevents infection by blocking attachment of pathogens tg mucosal Surface of tareet cells.
 Sulphated and sulponated polymers such aS PC-515 (carrageenan), Pro-2000, and Dextrin 2 Sulphate.

 Antiretroviral agents prevent HIV from replicating in the cells.
Anti-HIV antibodies combat pathogens before infection occurs.
 Antiretroviral agents include PMPA gel.
Plantibodies (anti-HIV antibodies genetically engineered from plants).

 Enhances naturally acidity of the vagina.
Supplements production of hydrogen peroxide.
Both mechanisms are hostile to pathogens, including HIV.
 Buffer Gel and Acidform help maintain natural levels of acidity )n the presence of semen.
Suppositories containing lactobabillus—which live normally in the heaLthy vagina—produce hydrogen peroxide.


The'Pill'
Oral contraceptives were introduced in the market in the 1960s heavily promoted by governments and pharmaceutical companies, and used extensively by hundreds of thousands of women all over the world. Over the next decades various problems came to light. Agitations by women's and health organizations forced confinements in the form of lower doses and combination pills. Ironically, manufacturers use` this to argue that 'post-marketing surveillance', involving So many women had made the pill much safer. They did nod admit that the drug had not been properly researched in the first place.
Today, the oral contraceptive is the most researched and refined contraceptive in the market - though this research followed its introduction, instead of preeceding it. As a result, it has now acquired the status of a 'gold standard': the risk factors identified over the years are measured against the use of other contraceptives.
However, these research findings are not used correctly in India. It has been proposed for official over-the-counter sale, despite the potential dangers. It is part of the government's 2ociaL marketing program, by which neighbourhood women go door to door and convince other women to buy the contraceptive. The marketers are given incentives based on the quantity sold, To the buyers, the pill has presented as a cheap contraceptive, available at their doorstep.[27]
Reports suggest that the practice violates all the recommendations emanating from research. women are not told of its side effects, the contraindications based on user age and health conditions. They are not told clearly that the pill is not to be used as the First contraceptive method.
Injectables
For oral contraceptives to Work, they must be taken regularly. A search was made for a 'user-independent' drug old drug-delivery method, which should maintain a steady concentration of the necessary hormones at the required levels, and for a length of time* This led to the development of injectable contraceptives.
Injectable contraceptives did not get US FDA approval for almost 20 years, mainly because of evidence, in the WHO's multi-center trial, of a carcinogenic effect. The problem wa3 bypassed when the WHO changed its directives for contraceptive research, holding that evidence from animal studies was not fully indicative of a contraceptive's side effects. These trials, conducted mainly in the third world, eventually concluded that injectables were relatively safe, but the details of the clinical trial's results were not made public.
For this reason, women's groups filed a petition asking for a ban pending the release of clinical trials results. Though this petition is in the court, injectables have been introduced in the Indian market for 'post-market surveillance'. [29]
Post-marketing surveillance is now replacing phase III and phase IV trials, particularly for contraception.  The protocol of post marketing surveillance requires the provision of a quarterly monitoring report. However, state drug controllers have not been issued directives asking for such reports.
Norplant
Various centres for research in human reproduction around the country are conducting what is being called the Phase III trials for NorPlant. [30]
An earlier, two-rod version of Norplant  had already undergone Phase III testing in India. However, the manufacturers were forced to stop producing the silastic material dnr the rods because of fears of its carcinogenic effect on workers who would be exposed to large quantities of the material. Rather than spend on research to confirm or dismiss this fear, the company stopped production, and attention turned to the six-rod Norplant  made of a different material. In 1992, the ICMR announced phase IV trials of Norplant. They argued that the progestin released by the two implants was identical, which meant the results of phase III trials of Norplan4-2 could be applied to the six-capsule Norplant [31]
Anti fertility vaccines

The most recent of fertility-controlling technologies is the anti-fertility vaccine (AFV), which works by inducing auto-immunity of some kind. Serious concerns have been voiced about its possible impact on the spread of HIV and other infectious diseases. It is also  know that women are more prone to developing autoimmune diseases. Yet researchers doing AFV research argue there is no scientific evidence to indicate whether an AFV, person, would increase or reduce the risk of HIV infection, except that it is a non-barrier method. [32]
Proponents of the AFV believe that it can ride on the poptlarity of immunization programmes. Their concern is to reduce births, but they do not discuss is potential, for Abuse,  Given people's vulnerability, and lack of access to information, it is entirely possible that an AFV could be administered without their knowledge, even under the guise of a disease control vaccine. This is not far-fetched when Indian women are sterilised or have IUDs inserted into them without their knowledge and permission. Sterilization It is only recently that the long-term, physiological side effects of sterilization are being discussed. With attention foccused on targets and camps.
Though even the WHO called for toxicological studies on animals before testing quinacrine insertion as a sterilization method, it is being used by private practitioners in India. The government of Karnataka has given permission to introduce quinacrine in its program. Thousands of women have been exposed to this mutagenic drug of doubtful efficacy. Why? Because as a chemical method, quinacrine does not elicit, in women, the fear associated with surgical interventions. In effect, women's fears are being used to introduce chemical methods unproven for both safety and efficacy. Various individuals, and women's groups, have raised legal challenges to the entry of quinacrine. [33]
  

TERMINAL METHODS
Voluntary sterilization is a well-estabished contraceptive procedure for capsules desiring no more children.it is a one time method, it does not require sustained motivation of the user for its effectiveness, provides the most effective protection against pregnancy. [34]
 Male sterilization
Male sterilization or vasectomy being a comparatively simple operationcan be performed even in primary health centres by trained doctors under local anaesthesia. When carried out under strict aseptic conditions, it should have no risk of mortality.In vasectomy, it is customary to remove a piece of vas at least 1 cm after clamping. The ends are ligated and then folded back on themselves and sutured into portion so that the cut ends face away from each other.This will reduce the risk of recanalisation at a later date.It is important to stress that the acceptor is not immediately sterile after the operation, usually until approximately 30 ejaculations have taken place. During this intermediate period another method of contraception must be used.If properly performed, vasectomies are almost 100 percent effective. [35]
 Female sterilization [36]
It can be done as an interval procedure, postpartum or at the time of abortion. Two procedures have become most common,they are
Laparoscopy:
This is a technique of female sterilization through abdominal approach with a specialized instrument called “laparoscope”. The abdomen is inflated with gas(carbon dioxide, nitrous oxide or air) and the instrument is introduced into the abdominal cavity to visualize the tubes. Once the tubes are accessible, the Falope rings are applied to occlude the tubes. This operation should be undertaken only in those centres where spwcialist obstetrician-gynaecologists are available. The short operating time, shorter stay in hospital and a small scar are some of the attractive features of this operation.

Minilap operation
Minilaparotomy is a modification of abdominal tubectomy. It is a much simpler procedure requiring a smaller abdominal incision of only 2.5 to 3 cm conducted under local aneaesthesia. The minilap technique is considered a revolutionary procedure for female sterilization. It is also found to be a suitable procedure at the primary health centre level and in mass campaigns. It has the advantage over other methods with regard to safety, efficiency and ease in dealing with complications. Minilap operation is suitable for postpartum tubal sterilization.
The Norplant system vas approved by the US Food and Drug Administration on December 10, 1990. This system has been approved for use in 14 countries and is currently in clinical trials in 35 other countries. The Norplant is a long-term reversible Contraceptive, lists for 5 years, and any time during those 5 years it can be discontinued. The Norplant consists of 6 soft flexible Silastic capsules that are placed in a fanlike pattern under the 1kin ob the upper arm, done under oral anesthesia in an Office or clinic. The procedure takes about 10-15 minutes. It works by continuously releasing a synthetic hormone, Levonorgestrol (progestin), that inhibits ovulation, cause3 eggs found to be released regularly, and thickens cervical mucus. Thickening of the cervical mucus makes it more difficult for sperm to reach the egg
 There is an estrogen used with this system. The Norplant system compares with oral contraceptives for effectiveness with this system .6 pregnancies occurrad/1000 women by the end of 1 year; over 5 years the total rate was 1.5 pregnancaes/100 users. If placed within 7 days after the onset of menstrual bleeding or immediately following an abortion, Norplant is effective within 24 hours. A backup method is necessary for the remainder of the cycle if it is 0laced during other times. After removal the contraceptive effect ends quickly and previous level of fertility is obtained. The capsules are not noticeable unless the woman is very thin or muscular. However, the outline of the Capsules can be felt and once placed they will break or move around. There will be a very small scar left, which is not noticeable in most women. Discoloration may occur over the site, but once the Norplant is removed it disappears. Some common side effects of the Norplant system are: menstrual changes, such as midcycle bleeding or spotting, irregularity, more frequent periods, heavier or lighter flow, or amenorrhea. Other side effects reported have bean headaches, weight gain, nausea and dizziness, change in appetite, enlargement of ovaries and fallopian tubes, mastalgia (breast tenderness), altered hair growth, and decreased libido. Even with these side effects a continuation rate of about 80% has been reported among women after the 1st year. This system works well for women who are considering sterilization but are not quite ready to make a final decision. Also, for women who want a long-term reversible contraceptive, who want to avoid daily contraceptive methods, and who cannot use or wish to avoid using estrogen-containing contraceptives. Women who have a history of acute liver diseases, unexplained vaginal bleeding, breast cancer, or blood clots in the legs, lungs, or eyes should consult their doctor prior to using this method. Also, women who are or think they are pregnant should not have the capsules placed. Postpartum women can safely have the capsules placed, but breast feeding mothers should wait at least 6 weeks prior to having the procedure done. [37]
Seasonale
 Seasonale, is a newer birth control pill that is similar to others in that it is 99% effective when taken as directed, uses the same type of hormones, is a once-daily pill, and has similar side effects. What makes Seasonale different from other birth control pills is that it has 3 months of active pills, instead of 3 weeks. This extends the time between your scheduled periods and lets you have only 4 periods per year. If you are taking Seasonale, you are likely do experience breakthrough bleeding ob spotting. Seasonale is available by prescription at University Health Services.
Extra-low-Dose Birth Control Pills
The newest pill, Yasmin, is the latest low-dose birth control pill. Similar to Alesse, Loeqtrin, and Cyclessa, this pill is 99% effective when taken correctly and helps decrease the amount of PMS water retention. As with all hormonal methods, you increase your risk of heart attacks and blood clots.
The Contraceptive Sponge [38]
 The Today Sponge  has returned to the market after receiving approval from the fda. the sponge cab be inserted hours before a woman has intercourse and remain in her body for up to 24 hours. it also contains spermicides that may offer some protection against itis and is 72% to 84% effective at preventing pregnancy, depending on whether you have had children or jot. the sponge can be purchased at health services pharmacy.

Vaginal Ring [39]
 Nuvaring is a new hormonal method that is similar to a diaphragm in that it is a flexible plastic ring, but instead of having to insert it before each act of intercourse and remove it 6 Hours later, it is left in place for 3 weeks. The ring emits progestin and estrogen and as about 99% effective at preventing pregnancy. Inserting nuvaring correctly will be a key factor in insuring its effectiveness. Because it is a hormonal method, it has similar risks that are associated with birth control pills. It costs about $35 a month. It is available at Health Services, talk to your medical provider if you are interested in trying this method.
Hormonal IUDs [40]
Mirena is a new hormonal iud, similar to the progastasert iud. the advantage is that mirena also emits the hormone progestin as an extra level of contraceptive protection. Iuds offer a high level of protection (approxima4ely 99%) but this method is not advised for women who haven't had children yet. It costs about $350 to $400 plus the cost of insertion, and although it is not available at ealph services, a medical provider may give you a referral to a site where it is available.

Single Rod Implant [41]
  Implanon, is a single rod (Hormonal implant method) that is placed. Norplant, a multiple rod implant which is no longer available in the US. Amplafon is a thin, flexible plastic implant about the size of matchstick, which contains the synthetic hormone progestin, Inserted under your upper arm, it can be left in place for up to 3 years. A woman won't be able to see the rod, unless she is very thin, but she can feel it with her fingers. Researches estimate that Implanon will be upto 99.9% effective for up to 3 years. Irregular bleeding is the most common side effect. Periods become fewer and lighter for most women and, in times, may stop altogether. Some women will have longer and heavier periods and some may have increased irregular or breakthrough bleeding. Implanon costs about $600, plus the cost of insertion. Implanon is not currently available at Health Services, but a medical provider may give you a referral to a site where it is available.

Male contraceptives
The development of cont2aceptive methods for men poses a different challenge because men are continuously producing sperm and therefore are continuously fertile, unlike women who have a limited number of fertile days each month. The current research is focused on developing contraceptive injections, implants, or vaccines that will reduce a male’s sperm count low enough to levels unlikely do cause pregnancy, but without damaging lifetime sperm production. Tests are currently being conducted overseas and the information if this field will continue to be expanded.
What is the female condom?
The female condom, the first condom-like device designed for women, was approved by the FDA in May 1993 for sale in the US [42]
It is a loose-fitting, pre-lubricated, 7-inch polyurethane pouch that fits into the vagina. It is a barrier method of birth control, which if used correctly, can prevent semen from being deposited in the vagina. It can also protect women against several sexually transmitted infections (STIs), including HIV, by preventing the exchange of fluids (semen, vaginal secretions, blood).
In the US it is sold under the name "Reality." This same product is sold under different names in other countries. It is available without a prescription in most major drug stores, although it may be somewhat difficult to find.. It is sold in packs of 3 or 6 and costs $2 to $3 dollars per condom. Reality female condoms are available at Health Education, which is on the 3rd floor of Health Services.
How is it used?
There is a flexible ring at the closed end of the thin, soft pouch. A slightly larger ring is at the open end. The ring at the closed end holds the condom in place in the vagina. The ring at the open end rests outside the vagina. If the condom is correctly placed in the vagina, it should form a "lining" against the walls of the vagina. The female condom can be put in up to 8 hours before sex. Follow these instructions for inserting it:
Find a comfortable position. Three possible options are standing with one foot on a chair, squatting with your knees apart or lying down with your legs bent and knees apart.
Hold the female condom with the open end hanging down. Squeeze the inner ring (at the closed end) with your thumb and middle finger and insert it into the vagina just past the pubic bone, much like a diaphragm or cervical cap. This inner ring lies at the closed end of the sheath and serves as an insertion mechanism and internal anchor. Make sure the condom is inserted straight and not twisted into the vagina.
The outer ring forms the external edge of the sheath and remains outside the vagina after it is inserted. Once in place, the device should cover the woman's labia and the base of the penis during intercourse.
During sex, it may be helpful to use your hand to guide the penis into the vagina inside the female condom. It is important that the penis is not inserted to the side of the outer ring. If the condom seems to be sticking to and moving with the penis rather than resting in the vagina, stop and add lubricant (K-Y jelly, Surgilube, Astroglide) to the inside of the condom (near the outer ring) or to the penis.
Female condoms should not be used simultaneously with male condoms because the friction between the two condoms may cause the condoms to break.
To remove the female condom after intercourse:
* Squeeze and twist the outer ring to keep the semen inside the pouch.
* Remove it gently before you stand up. Wrap it in a tissue and throw it away in the garbage. Do not flush it down the toilet.
Do not reuse female condoms. Use a new one every time you have intercourse. Be careful not to tear the condom with fingernails or sharp objects.
How effective is the female condom in preventing pregnancy and STIs?
Studies of the Reality condom show that it provides similar protection against pregnancy as other barrier methods, such as the diaphragm. If used perfectly, 5% of women will experience a pregnancy within the first year of use. In typical use (which includes imperfect insertion and inconsistent use), 21% of couples will experience a pregnancy within the first year. The rate of breaks or tears in the female condom is less than 1%, compared to 4% with the male condom.
Like the male condom, the female condom does not provide complete protection against all STIs. Infections such as herpes or HPV (genital warts) may still be transmitted by organisms on areas of the skin that are not covered by the condom.

What are the benefits?
The female condom provides an opportunity for women to share responsibility for the use of condoms with their partners.
* A woman can use the female condom if her partner refuses to use condoms.
* The polyurethane is less likely to cause an allergic reaction than a male latex condom. It also tears less often.
The female condom is available over the counter without a prescription. Unlike a diaphragm, it does not need to be fitted by a medical provider (one size fits all).
* The female condom will protect against most STIs if it is used correctly. It also covers much of the vulva for additional protection in that area.
* The outer ring of the female condom stimulates the clitoris during intercourse.
* The female condom can be used for protection against STIs during oral sex. Its design allows tongue insertion and fingering of the vagina or anus. If using the female condom in the anus, remove the inner ring before insertion.
* It can be inserted up to 8 hours before sex so it does not interfere with "the moment."
* The polyurethane is thin and conducts heat well so sensation is preserved.
What are the disadvantages?
* The outer ring is visible outside the vagina, which makes some women self-conscious in front of their partners.
* It makes crackling and popping noises during intercourse. Extra lubricant may help this problem.
* It has a higher failure rate than non-barrier methods such as oral contraceptive pills.
* It is somewhat cumbersome to insert.
* Each female condom can be used just once and is relatively expensive.
What are cervical caps and shields? The cervical cap is a rigid, thimble-shaped cup made of latex rubber that fits over the cervix and is held in place by suction. The cervical cap is slowly being phased out and replaced with the Fem Cap. The Fem Cap is a silicone cup shaped like a sailor's hat that fits securely in the vagina to cover the cervix. Lea's Shield is also a silicone cup with an air valve that fits snugly over the cervix and has a loop to help remove it. As with a diaphragm, it is necessary to use a small amount of spermicidal cream or gel with each method.
How do they work?
Each method acts as a physical and a chemical barrier, similar to the diaphragm, to prevent sperm from entering the uterus and fertilizing an egg. They must be used with spermicidal cream or jelly which helps inactivate sperm.
How effective are they in preventing pregnancy and STIs?
For cervical caps, [43] the typical pregnancy rate (which includes imperfect insertion and inconsistent use) for users who have never given birth is 16% per year; the perfect use rate is 9% per year. Pregnancy rates for women who have given birth are 32% for typical use and 26% perfect use. The difference in rates is because the cervix is bigger after childbirth and the cap may not fit as well.
For Fem Caps, the pregnancy rate for perfect use is not available, but for typical use the rate is 14%.
For Lea's Shields, the pregnancy rate for perfect use is not available, but for typical use the rate is 15%.
It is important to consider that none of these methods offer any protection against sexually transmitted infections (STHs).

 PHOTOGRAPHS/ MOA

 SIDE EFFECTS-DOSE RELATED
. Some common side effects of the Norplant system are: menstrual changes, such as midcycle bleeding or spotting, irregularity, more frequent periods, heavier or lighter flow, or amenorrhea. Other side effects reported have been headaches, weight gain, nausea and dizziness, change in appetite, enlargement of ovaries and fallopian tubes, mastalgia (breast tenderness), altered hair growth, and decreased libido. [44]
* Toxic Shock Syndrome (TSS) is a very rare but serious disorder. Patients should be aware of danger signs. Risk of TCS may be decreased by avoiding use of these methods cap during menstruation.
* Possible allergic reaction to the spermicide or to the rubber may occur.
* Some medical providers fear that the continued contact of the cervix with. The rubber and spermicide might cause the cervix  to become irritated. Women with cervical erosion, laceration or an abnormal pap smear should not use these methods until the conditions are resolved.
*several iuds cause pelvic infections[45] and uterine perforations.[46]
* Another concern is because cervical secretions build up in the cap or shield instead of bathing the vaginal wall. Some medical providers feel that free flow of cervical secretions is important in preventing infections. [47]

FAILURE RATE
Typical Contraceptive Failure Rates

 
TYPE FAILURE RATE
Implants and injectables 2-4%
Oral contraceptives. 9%
Spermicides 28%
Diaphragm and cervical cap 13%
Male condom. 15%

Who is Most at Risk for Contraceptive Failure?
Cohabiting women.
Unmarried women.
Women who live below 200% of the poverty level.
Black women.
Hispanic women.
Adolescents.
Women in their 20's.
The success or failure of various methods of birth control vary according to several factors. An example can be seen in a recent article in the Journal of the American Medical Association (JAMA) that said "...adolescent women who are not married but are cohabiting experience a failure rate of about 47% during the first year of contraceptive use, while the 12-month failure rate among married women aged 30 and over is only 8%."  [48]
The failure rate for Black women is about 20% and apparently does not vary with income, while Hispanic women experience a 12-month failure rate of 16% and white women about 11%--rates that do vary by income and which are significantly higher among poorer women and lower among financially secure women.
Why Does Contraception Fail?
The reasons for contraceptive failure are complex and vary according to method:
Oral contraceptives may fail if a woman forgets to take them every day at the same time or if 2 or more pills are missed during a cycle and an alternative method of birth control is not used.
Diaphragms and cervical caps can be moved out of place by the penis thrusting against the cervix.
Condoms can break and or semen can leak from them: Period abstinence, or natural family planning, can fail if a woman does not accurately predict her fertile period: IUDs can be dislodged. [49]
Withdrawal can fail if pre-ejaculatory semen enters the cervix or if the man is unable to withdraw his penis before ejaculation.

SUCCESS RATE
Fifty-three percent of unplanned pregnancies occur in women who are using contraceptives. When choosing a method of birth control women often consider the published success failure rates for the method they are considering. However, these rates are based on "perfect use" by women--that means using the method exactly as prescribed during every act of sexual intercourse.
Success rates for chemical and mechanical methods of contraception  [50]
    
Method Theoretical
Success rate (%)  User
success rate (%)
    
Combined pill  99.5 95 - 99
Mini-pill 97 - 99  93 - 99
IUD 94 - 99  93 - 98
Condoms 95 - 99  80 - 93
Diaphragm/cap (plus spermicide)  92 - 98  80 - 97
Vaginal Ring  96 96
Spermicide (chemical)  85 - 95  70 - 85
Spermicide (vitamin C)  96 96
Withdrawal 90 70 - 85
Injections (Depo-Provera) [51] 99 99
Skin Implants (Implanon) 99 99
Sterilization (male & female)  99.5 - 99.9  93 - 99.9
  
Theoretical success rate means that rate attainable if the method is used correctly 100 per cent of the time, in other words, only accounting for method failures.  
User success rate means that rate actually recorded from users. [52]  

Basic science research leads towards male fertility regulation [53]
All basic science research related to male reproductive physiology may – eventually – be related to contraceptive development or to the treatment of infertility. However, in a portfolio geared toward the development of male methods of contraception, it is important to focus on goal-oriented or applied research that is closely related to product development. Research on the molecular and cellular aspects of spermatogenesis/spermiogenesis, the acquisition of sperm-fertilising capacity, or identification of potential new targets for fertility regulation during the development of sperm or during acrosome and flagellar formation, for example, can help identify important events in the process of spermatogenesis and ways in which they can be targeted for male contraception. Specific examples and relevant results of targeted research activities will be discussed in the lecture.

ACCEPTABILITY AND BEHAVIOURAL STUDIES
Contraceptive acceptability and use are related to method and user factors13. Surveys have indicated that many men do believe that they should share responsibility of family planning and contraception with their partners, and men whose wives have experienced side effects from female methods of contraception may be even more concerned about shared responsibility. Indeed, many men who participate in male contraceptive clinical trials report that their main reason for participating was that the female partner had experienced problems with her method of contraception. [54]
In the evaluation of the safety and efficacy of any new technology, it is important to carry out acceptability studies and assessments of emotional, mental and behavioural changes during the course of clinical testing. Both qualitative and quantitative methodologies are being used to collect information on contraceptive use acceptability, family size preferences, decision-making regarding contraceptive use, and perceptions on male contraceptives, including side effects and mood, and behavioral and cognitive end points. Focus group discussions and some in-depth interviews have been carried out with the partners of men taking part in the contraceptive trials. Instruments are being developed to assess changes in sexual behaviour, if any, among the participating men.
WHO has supported several studies in various settings to collect, develop, adapt and validate a novel range of psychometric tools that can assist researchers to quantify changes in mood and behaviour (especially aggression) in healthy adult men who are participating in contraceptive clinical trials. In addition to more traditional instruments to collect data on method acceptability, a male aggression questionnaire and a partner questionnaire, to assess the female partner’s perceptions of any behavioural changes, have been developed. Some results of acceptability research have been described above (e.g. TU injections in Chinese men as a potential method of hormonal contraception). Acceptability and social science research related to novel technologies, users, service delivery systems and public policy will continue. [55]

CONCLUSIONS
Available scientific data suggest that the prospects of reversible male contraception appear promising. There is strong evidence that an androgen, with or without a progestin, can provide effective contraception and is well tolerated. Agencies continue to promote research towards acceptable contraceptive methods for use by men. Such research can focus on: [56]
inhibition of sperm production• interference with sperm function and structure
interruption of sperm transport
interruption of sperm deposition
prevention of sperm-egg interaction.
Meanwhile, discussions are under way with some pharmaceutical companies to ensure the continued development and testing of hormonal male contraceptives and to ensure their availability at low cost to the public sector in developing countries.

 

NEED/PRESENT SCENARIO
Contraceptive research is directed at control over women's fertility. It is based on a reductionist view of the human body. However, our physiologies are complex, consisting of various interdependent systems. Tapering with one affects all the others. Women's hormonal systems have been tampered with extensively through population control programmes over the last 35 years. [57]
Any reorientation of contraceptive research must involve a stop to research on methods such as AFVs. This may be seen as anti-progress, anti-development, and interfering with the noble pursuit of acquiring scientific knowledge. However, women have suffered the consequences of this unchecked 'development' and 'noble pursuit' for too long. It is time to redefine what is meant by progress, and aim for knowledge that would help us as users of such technologies.

PRESENTLY AVAILABLE

A Yale researcher who invented a test to determine whether a woman's endometrium (uterine lining) is healthy and ready for embryo implantation has identified two new biochemical markers that improve assessment of the endometrium.
The endometrial function test (EFT®) was created by Harvey J. Kliman, M.D., a research scientist in the Department of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine. An abnormal EFT is associated with pregnancy failure, while a normal EFT is associated with pregnancy success. Kliman's study, published in the July issue of the journal Fertility and Sterility, identifies two new biochemical markers, cyclin E and p27, that more accurately assess endometrial health compared to the routine examination that is done by pathology laboratories.
"These findings will help women who have difficulty conceiving become pregnant at a reduced cost," said Kliman who likens the endometrium to soil and the embryo to a treasured plant. "Soil has to be tested and prepared in order for the plant to grow in it. The endometrium also has to be healthy and capable of supplying the appropriate nutrients for the embryo. If the right conditions do not exist, implantation will not occur. This test, which uses these new biochemical markers, will improve assessment of the endometrium."
Kliman said the most difficult step in the process of conception is the attachment (implantation) of the embryo to the endometrium. Abnormalities in the process of implantation are believed to be the basis of many cases of unexplained infertility in women. A normal healthy endometrium will make many different substances (markers). By measuring several of these markers in endometrial biopsies, researchers can determine if the endometrium is receptive to implantation. Kliman said the two new markers he used in his study are more effective at assessing endometrial health than the other markers studied to date or methods in current use.
"It is important that patients and doctors know that this test is available," said Kliman. "The EFT helps a patient and doctor figure out what the next steps are when assisted reproductive technology procedures don't appear to work. The test is done only at Yale, and we currently receive biopsies from all over North America for evaluation."
In this initial study, Kliman and his colleagues looked at 33 fertile volunteers, 83 women seeking fertility treatment, and 23 women undergoing mock cycles in preparation for frozen or donor embryo transfer. The researchers compared the expression of cyclin E and p27 in these groups at many different times throughout the menstrual cycle to establish the normal and abnormal patterns of expression of the markers in the endometrium.
The endometrium is made up of stroma and glands. The endometrial stroma is the tissue that supports the glands and holds the endometrium together, much like the cake supports the fruit in a fruitcake. "Fertile women expressed cyclin E in their glands up to about cycle day 19, and then did not have any after that," said Kliman. "Infertile women, on the other hand, much more frequently expressed cyclin E well after cycle day 19, often to the end of their cycles. The stroma in both groups was the same. These results suggest that infertile women have a defect in the way the stroma communicates with glands."
Kliman said a normal endometrium is like a surfer and a wave she has caught -- with the wave being the stroma and the surfer the glands. "Just as the surfer will miss the wave if it goes by too quickly, the endometrial glands can be left behind if the stroma moves too quickly," said Kliman. "This is what happens in many women with unexplained infertility. The EFT can diagnose this problem and help guide the infertility specialist to fix the problem, which in turn will improve the chances of implantation and a successful pregnancy."
Kliman's group is currently awaiting the final clinical outcomes from over 800 patients who have had EFTs to determine the statistical significance and predictive value of a normal versus abnormal EFT result. [58]


Contraceptives that are readily available and acceptable are required in many poorer countries to reduce population growth and in all countries to prevent maternal morbidity and mortality arising from unintended pregnancies. Most available methods use hormonal steroids or are variations of barrier methods. Reports from several fora over the last 12 years have emphasized the number of unwanted pregnancies and resultant abortions, which indicate an unmet need for safe, acceptable, and inexpensive contraceptive methods. This unmet need can be assuaged, in part, by development of new nonhormonal contraceptive methods. This Review addresses the contribution that the "omic" revolution can make to the identification of novel contraceptive targets, as well as the progress that has been made for different target molecules under development. [59]


Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10),8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg-1. [60]

To determine the safety and acceptability of use of Carraguard, a carrageenan-derived candidate microbicide gel, during sexual intercourse in women and men. Trial was conducted for a 6-month randomized, placebo-controlled  among sexually active, couples at relatively lower risk for HIV infection in northern Thailand. Women inserted 1 applicator of study gel vaginally every time the couple had sex. Safety was assessed by symptom report and genital examination of both partners and by changes in vaginal flora. Acceptability was assessed by participant interview. Overall, 55 couples were randomized, 28 to Carraguard use and 27 to the methyl-cellulose placebo gel group. Retention and study gel use were similarly high in both study groups; use of gel without condoms was reported in more than 95% of vaginal sex acts. The 2 study groups were similar in the proportions of women and men with symptoms or with genital findings without epithelial disruption, of men with findings with epithelial disruption, and of women with abnormal genital flora, whereas more women in the placebo group had findings with epithelial disruption. Women and men in both groups reported that the gel and applicator were acceptable. Carraguard can safely be used an average of 2 to 3 times per week during sex and is acceptable to Thai women and men. [61]


 Study was conducted for to explore the plausible pathway of Chenopodium album seed extract (CAE)-mediated sperm cell death. The role of CAE for its spermicidal action was assessed by (a) measuring lipid peroxidation, protein carbonyl content and intracellular glutathione content in CAE exposed sperm cells; (b) assaying antioxidant enzymes like catalase and superoxide dismutase (SOD); (c) analyzing protein expressions by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis; (d) fluorimetric measurement of intracellular H2O2 level and generation of reactive oxygen species (ROS) in CAE-treated sperm cells; and (e) DNA ladder formation study. CAE-induced sperm death is due to (a) lipid peroxidation of the sperm cell membrane, oxidation of some critical cellular proteins and depletion of intracellular reduced gluthathione, indicating production of ROS; (b) activation of Mn-SOD and inactivation of catalase favoring endogenous accumulation of H2O2; (c) generationof O2 at an enhanced rate during oxidative stress as evidenced by increased Mn-SOD activity and protein expression; (d) accumulation of ROS in spermatozoa reflected in the fluorimetric experiments; and (e) increased production of O2 and H2O2 induced apoptosis-like death in sperm cells as observed by DNA ladder formation. The sperm death mediated by CAE is due to oxidative damage of cellular macromolecules by in situ generation of ROS. [62]

As the world's population continues to soar, contraception has become increasingly important. Recently, men have expressed willingness to share the burden of family planning. Thus, safe, effective and reversible male contraceptives would satisfy an urgent need among couples. Currently, there are several promising non-hormonal contraceptives at various stages of research and development. In addition, major advances in genomic and proteomic research have been instrumental in identifying and characterizing genes and proteins expressed uniquely in the testis or other male reproductive organs, which might become 'druggable' targets for non-hormonal male contraceptive development in the future. Through committed research, advocacy and support, male contraceptives are likely to become a valuable addition to the current choices of family planning. [63]


 Many formulations of OCs are now available. Monophasic preparations contain the same amount of EE and progestin and are taken for 21 days of each 28-day cycle. Biphasic and triphasic preparations take the form of two or three types of pills, with varying amounts of active ingredients. Biphasic and triphasic OCs have been formulated so that the amount of progestin is reduced and the effects correspond more closely to hormonal influences during natural menstrual cycles. Recently, several formulations of continuous daily regimens of ethinylestradiol (10 microg and 30 microg) and a progestin have entered the market. These formulations allow withdrawal-bleeding periods only 4 times a year. A yearly, no-cycling version of levonorgestrel and EE (Lybrel) received FDA approval in May 2007. There are a limited number of progestin-only contraceptives. These contraceptives are the mini-pill containing norethindrone, norgestrel, or levonorgestrel; a subdermal implant of norgestrel (Norplant II); intramuscular and subcutaneous preparations of medroxyprogesterone acetate and norethindrone enanthate, administered every 3 months; and intrauterine devices that release progesterone and levonorgestrel. [64]

Contraceptive vaccines can provide valuable alternatives to current methods of contraception. We describe here the development of sperm-reactive human single chain variable fragment (scFv) antibodies of defined sperm specificity for immunocontraception. Peripheral blood leukocytes (PBL) from antisperm antibody-positive immunoinfertile and vasectomized men were activated with human sperm antigens in vitro, and the complementary DNA prepared and PCR-amplified using primers based on all the variable regions of heavy and light chains of immunoglobulins. The scFv repertoire was cloned into pCANTAB5E vector to create a human scFv antibody library. Panning of the library against specific sperm antigens yielded several clones, and the four strongest reactive were selected for further analysis. These clones had novel sequences with unique complementarity-determining regions. ScFv antibodies were expressed, purified and analyzed for human sperm reactivity and effect on human sperm function. AFA-1 and FAB-7 scFv antibodies both reacted with fertilization antigen-1 antigen, but against different epitopes. YLP20 antibody reacted with the expected human sperm protein of 48 plus or minus 5 kDa. The fourth antibody, AS16, reacted with an 18 kDa sperm protein and seems to be a human homologue of the mouse monoclonal recombinant antisperm antibody that causes sperm agglutination. All these antibodies inhibited human sperm function. This is the first study to report the use of phage display technology to obtain antisperm scFv antibodies of defined antigen specificity. These antibodies will find clinical applications in the development of novel immunocontraceptives, and specific diagnostics for immunoinfertility. [65]

Spermicidal compounds that also exhibit antimicrobial properties would be extremely attractive agents as they could be used to not only prevent unwanted pregnancy but also to combat the growing prevalence of sexually transmitted infections (STI). One class of compounds that are potential candidates for development of dual-acting contraceptive products are antimicrobial peptides (AMPs). Herein, we report preliminary studies carried out to investigate the spermicidal activity of two bacteriocins, lacticin 3147 and subtilosin A, on bovine, horse/pony, boar and rat sperm. [66]

Published condom breakage studies typically report the percentage of failures but rarely provide any evidence on the mechanism of failure. Over a period of 7 years, broken condoms returned to a supplier (SSL, Durex) via consumer complaints were examined to determine the cause of failure. Also, some consumers who reported breakage but did not return condoms were sent a questionnaire on the causes of breakage. Finally, theories proposed for the mechanism of breakage were investigated on a laboratory coital model. Nearly 1000 (n=972) returned condoms made from natural rubber and polyurethane were examined. Visible features on those that were broken, were classified. Evidence combined from examining returns, questionnaire responses and the coital model strongly suggests a single predominant mechanism of failure we named "blunt puncture," where the tip of the thrusting male penis progressively stretches one part of the intact condom wall until it ultimately breaks. Blunt puncture appears to be the mechanism of breakage responsible for more than 90% of condom breakage not attributable to misuse. Knowledge of the main mechanism of breakage should help develop better userinstructions, better test methods and, ultimately, better condoms. [67]

Emergency contraception [68]
According to Anna Glasier Family Planning & Well Woman Services, Lothian Primary Care NHS Trust, 18 Dean Terrace, Edinburgh EH4 1NL, UK ,Knowledge and use of emergency contraception world-wide is extremely limited. Recent research has demonstrated that levonorgestrel alone is at least as effective as the Yuzpe regimen and is much better tolerated. Levonorgestrel is likely to become the method of choice in the early 21st century. Mifepristone is highly effective even at doses which are not abortifacient. Efficacy cannot be calculated precisely, but all presently available methods seem to prevent at least 74% of unwanted pregnancies. The Yuzpe regimen inhibits or delays ovulation, but there is no good evidence that it prevents implantation. There are no data on the mechanism of action of levonorgestrel alone and the mode of action of mifepristone depends on when in the reproductive cycle it is used. Accessibility to emergency contraception is limited by the requirement for it to be prescribed by a doctor Advanced provision of emergency contraception may prevent a significant number of unwanted pregnancies.

STASTICAL EVALUATION

 The evaluation of contraceptive methods is based on use-effectiveness .This is expressed in terms of “failure rate per hundred woman years of exposure(HMY). This rate is also known as”Pearl Index”. It was developed by Raymond Pearl, and is normally used for studying the effectiveness of contraceptive. The number of pregnancies includes all pregnancies, whether this had terminated as live births, still births or abortions or had not yet terminated. This rate is given by the formula: [69]


Failure rate per HMY  =   Total accidental pregnancies / total months of exposure * 1200.

In applying the above formula, total accidental pregnancies shown in the numerator must include every known conception, whatever is the outcome. The factor 1200 is the number of months in 100 years. The total months of exposure in the denominator is obtained by deducting from the period under review of 10 months for a full term pregnancy and 4 months for an abortion.

A failure rate of 10 per HWY would mean that in the life time of the average woman about one fourth or 2.5 accidental pregnancies would result, since the average fertile period of a woman is about 25 years, not 100 years.

In designing the and interpreting a use effective trial, a minimum of 600 months of exposure is usually considered necessary before any firm conclusion can be reached.

Rates of pregnancy and expulsion per 100 women after 12 months of iud use, by device. [70]

DEVICE PREGNANCY RATE EXPULSION RATE
Lippes loop c 3.0 19.1
Lippes loop d 2.7 12.7
Progestasert 1.8 3.1
Copper-7 1.9 5.6
Cu-t-200 3.0 7.8
Cu-t-200c 0.9 8.0
Nova t 0.7 5.8
Multiload 250 0.5 2.2
Multiload 375 0.1 2.1


Contraceptive Efficacy
In addition to issues with respect to accessing contraception, low income women have higher rates of contraceptive failure. A large population based survey in the United States showed that the contraceptive failure rate in low income women was 17%, compared with 9% in women with higher incomes. The study found 12 month failure rates as high as 32% for cohabitating women under 20 living in poverty who were using the oral contraceptive pill. [71]
Unintended Pregnancy
Women surviving on low incomes have higher rates of unintended pregnancy. This is not surprising, given the challenges they face in accessing contraception and consistently using it correctly.
In addition to higher rates of unintended pregnancy, a Toronto study found higher rates of sexually transmitted infections in those aged 15-24 living on low incomes.
Once pregnant, disadvantaged adolescents are less likely to have an abortion. Data from the city of Winnipeg showed that young women in the highest income quintile have higher rates of abortion and lower rates of live birth than young women in the lowest income quintile. [72]
Women from lower socioeconomic backgrounds are more likely to have a positive view of adoption as an option for the resolution of an unintended pregnancy.
Infertility [73]
Poor women (along with lesbians, single women, older women and women with disabilities) have traditionally been excluded from accessing assisted reproductive technologies.
Women with higher income and education do not experience higher rates of infertility. In fact, women in the lowest socioeconomic groups have the highest rates of infertility.
Couples and individuals who experience infertility often experience guilt, low self-esteem, depression, disappointment, increased rates of relationship conflict and sexual dysfunction.

How effective is the IUD in preventing pregnancy and STIs?
The IUD is one of the most effective methods of contraception available. The rate of pregnancy for women using the ParaGard is 0.8% and for women using the Progestasert the rate is 2%. However, IUDs do not offer any protection against sexually transmitted infections (STIs). [74]

 Oral contraceptives….. [75]
 Considering oral contraceptives, the combined type is the most efeective ie. 100 percent. In preventing pregnancy.Some women do not take pill regularly, so the actual rate is lower. In the developed countries,the annual pregnancy rate is less than 1 percentbut in many countries, the pregnancy rate is considerably higher.
Under clinical trials, the effectiveness of progestogen- only pills is almost as good as that of the combination products.However, in large family planning programmes, the effectiveness and the continuation rates are usually lower than in clinical trials. The effectiveness may also be affected by certain drugs such as rifampicin, Phenobarbital and ampicillin.

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niyat  |  27-Jul-2010 17:18:19 IST
i m niyat.it is good information
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