FEMALE INFERTILITY- UNDERSTANDING CAUSES, TESTS AND TREATMENT

ABOUT AUTHOR:
Balram Soni*
M.Pharm., Ph.D. Scholar
Psychiatric Centre, S.M.S. Medical College, Jaipur, Rajasthan
*brpharma@rediffmail.com

ABSTRACT:
Studies indicate that slightly over half of all cases of infertility are a result of female conditions, while the rest are caused by either sperm disorders or unidentified factors. Infertility in female is very often observed. It is inability to conceive and produce the child. ART (Assisted Reproductive Technology) has been carried out such as IVF, ICSI but common people cannot afford the cost of such procedures. Various allopathic, Ayurvedic and other alternatives medicines and physiotherapy with acupuncture are been effective to enhance the pregnancy and these drugs and exercises will even prevent the recurrent abortions. In this regard the present review is aimed to provide all the necessary information regarding the effective method for treatment of female infertility.

REFERENCE ID: PHARMATUTOR-ART-1811

INTRODUCTION:
FEMALE INFERTILITY¹:
Infertility is a condition defined as not being able to become pregnant after at least one year of unprotected, regular, well-timed intercourse.

Many women may be infertile during their reproductive years but be completely unaware of this. Factors such as age, lifestyle and physical condition contribute considerably to fertility problems. Pregnancy is the result of a process that has many steps. To get pregnant:

• A woman must release an egg from one of her ovaries (ovulation).
• The egg must go through a Fallopian tube toward the uterus (womb).
• A man's sperm must join with (fertilize) the egg along the way.
• The fertilized egg must attach to the inside of the uterus (implantation).

Any interference that occurs during this fertilization process may bring about infertility.

CAUSES OF INFERTILITY^2-5:
1. Ovulation disorders
Ovulation disorders account for infertility in 25 percent of infertile couples. These can be caused by flaws in the regulation of reproductive hormones by the hypothalamus or the pituitary gland, or by problems in the ovary itself. You have an ovulation disorder if you ovulate infrequently or not at all.

·         Hormonal causes: The two hormones responsible for stimulating ovulation each month — follicle-stimulating hormone (FSH) and luteinizing hormone (LH) — are produced by the pituitary gland in a specific pattern during the menstrual cycle. Excess physical or emotional stress, a very high or very low body weight, or a recent substantial weight gain or loss — for instance, 10 percent of your body weight — can disrupt this pattern and affect ovulation. The main sign of this problem is irregular or absent periods. Much less commonly, specific diseases of the pituitary, usually associated with other hormone deficiencies or with excess production of prolactin, may be the cause. Hypothyroidism: Many women that are diagnosed with hypothyroidism find it very hard to get pregnant due to irregular menstruations and the lack of ovulation. Hyperthyroidism: Just like hypothyroidism, the lack of releasing an egg while suffering with hyperthyroidism may make it impossible for women to get pregnant.

• Polycystic ovary syndrome (PCOS):In PCOS, complex changes occur in the hypothalamus, pituitary and ovary, resulting in overproduction of male hormones (androgens), which affects ovulation. PCOS can also be associated with insulin resistance and obesity.
• Luteal phase defect:Luteal phase defect happens when your ovary doesn't produce enough of the hormone progesterone after ovulation. Progesterone is vital in preparing the uterine lining for a fertilized egg.
• Premature ovarian failure:This disorder is usually caused by an autoimmune response, where your body mistakenly attacks ovarian tissues. It results in the loss of the eggs in the ovary, as well as in decreased estrogen production.

2. Damage to fallopian tubes (Tubal infertility)
When fallopian tubes become damaged or blocked, they keep sperm from getting to the egg or close off the passage of the fertilized egg into the uterus. Causes of fallopian tube damage or blockage can include:

• Inflammation of the fallopian tubes (salpingitis) due to chlamydia or gonorrhea
• Previous ectopic pregnancy, in which a fertilized egg becomes implanted and starts to develop in a fallopian tube instead of in the uterus
• Previous surgery in the abdomen or pelvis

3. Endometriosis
Endometriosis occurs when tissue that normally grows in the uterus implants and grows in other locations. This extra tissue growth — and the surgical removal of it — can cause scarring, which impairs fertility. Researchers think that the excess tissue may also produce substances that interfere with conception.

4. Cervical causes
Cervical narrowing or blockage, also called cervical stenosis, this can be caused by an inherited malformation or damage to the cervix. The result is that the cervix can't produce the best type of mucus for sperm mobility and fertilization. In addition, the cervical opening may be closed, preventing any sperm from reaching the egg.

5. Uterine causes
Benign polyps or tumors (fibroids or myomas) in the uterus, common in women in their 30s, can impair fertility by blocking the fallopian tubes or by disrupting implantation. However, many women who have fibroids can become pregnant. Scarring within the uterus also can disrupt implantation, and some women born with uterine abnormalities, such as an abnormally shaped (bicornuate) uterus, can have problems becoming or remaining pregnant.

6. Unexplained infertility
In some instances, a cause for infertility is never found. It's possible that combinations of minor factors in both partners underlie these unexplained fertility problems. The good news is that couples with unexplained infertility have the highest rates of spontaneous pregnancy of all infertile couples.

7. Miscellaneous

• Weight: Maintaining a healthy body weight is vital for fertility. Being overweight or obese combined with a lack of exercise leads to excessive fat deposition which may cause ovulation problems, resulting in infertility. A low body weight and chronic dieting are also associated with amenorrhea or loss of menstrual cycles, making it difficult for ovulation to occur.

• Stress: Highstress levels may interfere with ovulation and the body’s ability to conceive. When planning to fall pregnant, women should learn to manage their stress through relaxation techniques.

• Smoking: Smoking may affect your ability to fall pregnant. Women run the risk of developing cervical and tube problems, abnormal menstrual cycles, hormonal imbalances and when they do eventually become pregnant, an ectopic pregnancy may result. Generally, smokers take longer to conceive than non-smoking women.

• Sexually transmitted diseases (STDs): Infertility can sometimes be the result of sexually transmitted diseases (STDs) or infection. If you are planning on becoming pregnant, get tested for sexually transmitted diseases to prevent further fertility problems or spread of the disease.

DIAGNOSING FEMALE INFERTILITY⁶
The diagnosis of infertility in women is based on the physical symptoms as well as sexual history. It is also very important that a woman tracks her ovulation at home by recording her basal body temperature for several months, checking the texture of cervical mucus and using a home ovulation test kit.

Additional tests to determine infertility

• Blood tests to check hormone levels
• Ultrasound of the ovaries
• An endometrial biopsy to check the lining of the uterus

Two diagnostic tests that may be helpful in detecting scar tissue and tubal obstruction are hysterosalpingography and laparoscopy.

• Hysterosalpingography (HSG).This procedure involves either ultrasound or X-rays taken of the reproductive organs. Either dye or saline and air are injected into the cervix and travel up through the fallopian tubes. This enables the ultrasound or X-ray to reveal if the fallopian tubes are open or blocked.
• Laparoscopy.In this procedure, a laparoscope (a slender tube fitted with a fiberoptic camera) is inserted into the abdomen through a small incision near the belly button. The laparoscope enables the doctor to view the outside of the uterus, ovaries, and fallopian tubes to detect abnormal growths, as in endometriosis. The doctor can also check to see if the fallopian tubes are open at the same time.

HELP FOR FEMALE INFERTILITY^7-13
Once infertility has been diagnosed, there are a number of treatment options available depending on the root cause of the problem. These treatments are costly and generally based on the preference of both partners.

1. Natural Remedies General

• Fresh, organic fruits and vegetables
• Whole grains
• Dairy proteins, including milk, lassi, and panir (a fresh cheese made of milk)
• Mung dhal
• Soaked almonds or soaked walnuts (you can grind them and add them to your vegetables)
• Sweet, juicy fruits such as mangoes, peaches, plums, and pears
• Dried fruits such as dates, figs, and raisins
• Take plenty of Vitamin C to increase cervical mucus. Cervical mucus is very important when trying to get pregnant. Nitric oxide is another good resource to help increase cervical mucus as well as help blood flow to the reproductive organs.
• Take grape seed extract with Vitamin C to help make the Vitamin C more effective. Grape seed extract is an antioxidant and can help protect sperm.
• Take evening primrose oil to help increase cervical mucus and increase the quality of cervical mucus. When trying to conceive, ovulation usually occurs when the cervical mucus looks like egg whites. Evening primrose oil is an herb and is also used as an essential fatty acid and anti-inflammatory.
• Eat plenty of calcium rich foods such as milk, cheese and yogurt. Two to three servings a day of calcium-rich foods will help treat infertility.
• Maintain a diet rich in fresh fruits and vegetables. Fruits and vegetables that contain folic acid are especially important in treating infertility. Seven servings of fruits and vegetables every day is important. Foods that contain folic acid include spinach, broccoli, orange juice and lentils.

2. Home remedies for Female Infertility:

1. Jamun Leaves: To deal with the female infertility problem, you can eat jamun leaves. Add some honey in case you don’t like the taste of jamun leaves. 
2. Root of Banyan Tree:Roots of banyan tree are highly effective in curing the female infertility problem.Collect these roots and dry them I sun for few days. Then grind them and make fine powder from them. When your menstrual cycles are over after that on the first night have this powder with milk. Make sure that you don’t eat anything immediately after having this. Follow this remedy for about one year. There will be surely some good news waiting for you and all thanks to this simple and easy remedy.
3. Winter Cherry:This herb is also useful in the treatment of female infertility. Dry this herb and store it in powder form. After your menstrual cycle gets over start drinking 6 gram of this powder by putting it in one cup of milk. Do this for about one week and then again stop. Next month again follow the same procedure.  
4. Crud and Cheese:Include cheese and curd in your daily meal, as these two are effective in increasing the chances of fertility in women.
5. Egg Plant: Eggplant is effective in the treatment of female infertility. Cook this eggplant and have it with buttermilk. Try this remedy for about two months, as it will definitely help to cure female infertility problems.  
6. Yoga:Join some yoga class, as some of the postures of Yoga really help in curing female infertility. It is better to do these postures under the guidance of experienced teacher.
7. Vitamin C and Vitamin E:both these vitamins are very effective in increasing the chances of fertility in women. Apart from this zinc is also effective in cure of female infertility. 1000mg of vitamin C and 30 mg of zinc should be consumed on a daily basis.  
8. Diet:You must eat lots of green vegetables, fresh fruits, nuts, seeds, grains, milk, honey, curd, cheese, sprouts, beans, etc. All these things are needed for having a healthy body.
9. Dong Quai: It is a Chinese fertility herb that is helpful in dealing with menstrual difficulties. Dong Quai increases the chances of implantation by balancing level of estrogen.

3. Conventional Medicine
Infertility in womenmay be treated with fertility drugs, surgery, artificial insemination or assisted reproductive technology – however many of these treatment options may have negative side effects like premenstrual symptoms such as nausea, headaches and weight gain.

In addition, fertility treatments have also been known to increase a woman’s chance of having twins, triplets or other multiples. Your doctor may recommend surgery if your fallopian tubes are blocked or there are any anatomical defects. Surgery is also helpful if endometriosis, fibroids or ovarian cysts need to be removed.

Artificial insemination refers to a range of techniques in which the man's sperm is placed into the woman's genital tract artificially. Placing the sperm in the neck of the cervix is known as intra-cervical insemination. When sperm is introduced directly into the uterus itself, this is known as intrauterine insemination, IUI.

Assisted reproductive technology, ART refers to the various methods used to help infertile couples. It entails the removal of eggs from a woman’s body, then combining them with sperm in the laboratory and placing the embryos back into the body.

The different types of assisted reproductive technology include In vitro fertilization, IVF, zygote intra-fallopian transfer, ZIFT or tubal-embryo transfer, gamete intra-fallopian transfer, GIFT and intracytoplasmic sperm injection, ICSI.

Other methods of ART also include donor eggs and embryos or gestational carriers more commonly known as surrogate mothers. In vitro fertilization is the most popular and effective ART, with fertilization occurring outside the body. It is often used when a woman experiences ovulation problems or when her fallopian tubes are

Fertility drugs for women
The most popular fertility drugs for women are:

• Clomifene
• Gonadotrophins
• Bromocriptine

All these help ovulation to happen, but which drug is right for you will depend on the reason you're having difficulty ovulating and conceiving.

Clomifene citrate
Clomifene citrate blocks the effect of the hormone estrogen in your body. This blocking effect tricks your body into increasing the levels of two other hormones that are essential for ovulation. These two other hormones are:

• follicle-stimulating hormone (FSH)
• luteinising hormone (LH)

FSH causes the eggs in your ovaries to ripen, ready for release. LH triggers the release of one or more mature eggs from the ovary follicles. The egg or eggs then move down into one of your fallopian tubes.

You usually take clomifene in pill form for five days of your cycle, for up to six months. Brand names for clomifene citrate are Clomifene and Clomid.
Gonadotrophins
Luteinising hormone (LH) and follicle-stimulating hormone (FSH) are types of gonadotrophins. LH and FSH directly stimulate your ovaries to produce and ripen eggs.

You can have LH and FSH as a course of injections over about 12 days. The injections make your ovaries start to develop and mature egg follicles. The injections of LH and FSH will be followed by a final injection of another hormone, called human chorionic gonadotrophin (hCG)

LH and hCG tell your ovaries to release the egg (or eggs) that they have just developed. Both hormones are used in some fertility treatments, because both hormones have an action on your follicles. LH stimulates the follicle to release the egg. HCG ensures the follicle is in the right condition to release progesterone and therefore help to maintain a pregnancy.

There are several brand names for gonadotrophins. Merional and Menopur contain FSH and LH. Gonal F, Menotrophin and Puregon contain FSH only. Choragon and Pregnyl contain (hCG)

Bromocriptine
Bromocriptine is used to correct a hormonal imbalance that can prevent your ovaries from releasing an egg every month.

You might benefit from taking bromocriptine if you have too much of the hormone prolactin in your body. Too much prolactin reduces levels of the hormone estrogen.

This drug inhibits prolactin production. Prolactin stimulates milk production in breast feeding mothers. If non-pregnant, non-breast feeding women have high levels of prolactin they may have irregular ovulation cycles and have fertility problems.

You can take bromocriptine as tablets that you swallow or as capsules that you insert into your vagina. The brand name for bromocriptine is Parlodel.

Metformin(Glucophage)
Women who have not responded to Clomifene may have to take this medication. It is especially effective for women with PCOS, especially when linked to insulin resistance.

Injectable fertility drugs can sometimes be the victims of their own success and cause multiple births - when the woman gets pregnant she has twins, triplets, or perhaps more babies in one go. Oral fertility drugs also raise the risk of multiple pregnancies, but much less so than injectable ones. It is important to monitor the patient carefully during treatment and pregnancy. The more babies the mother carries inside her the higher is her risk of premature labor.

If a woman needs an HCG injection to activate ovulation and ultrasound scans show that too many follicles have developed, it is possible to withhold the HCG injection. Couples may decide to go ahead regardless if the desire to become pregnant is very strong.

Surgical procedures for women

*    Fallopian tube surgery- if the fallopian tubes are blocked or scarred surgery may repair them, making it easier for eggs to pass through them.

*    Laparoscopic surgery- a small incision is made in the woman's abdomen. A thin, flexible microscope with a light at the end (laparoscope) is inserted through the incision. The doctor can then looks at internal organs, take samples and perform small operations. For women with endometriosis, laparoscopy removes implants and scar tissue, reducing pain and often aiding fertility.

Assisted conception¹⁴

• IUI (intrauterine insemination) - a fine catheter is inserted through the cervix into the uterus to place a sperm sample directly into the uterus. The sperm is washed in a fluid and the best specimens are selected. This procedure must be done when ovulation occurs. The woman may be given a low dose of ovary stimulating hormones.
• IUI is more commonly done when the man has a low sperm count, decreased sperm motility, or when infertility does not have an identifiable cause. The procedure is also helpful for males suffering from severe erectile dysfunction.
• IVF (in vitro fertilization) - sperm are placed with unfertilized eggs in a Petri dish; the aim is fertilization of the eggs. The embryo is then placed in the uterus to begin a pregnancy. Sometimes the embryo is frozen for future use (cryopreserved). Louise Joy Brown, born in England in 1978, was the world's first IVF baby. Before IVF is done the female takes fertility drugs to encourage the ovaries to produce more eggs than normal.
• ICSI (Intracytoplasmic sperm injection) - a single sperm is injected into an egg to achieve fertilization during an IVF procedure. The likelihood of fertilization improves significantly for men with low sperm concentrations.
• Donation of sperm or egg- if there is either no sperm or egg in one of the partners it is possible to receive sperm or eggs from a donor. Fertility treatment with donor eggs is usually done using IVF. In the UK and a growing number of countries the egg donor can no longer remain anonymous - the offspring can legally trace his/her biological parent when reaching the age of 18.
• Assisted hatching- this improves the chances of the embryo's implantation; attaching to the wall of the uterus. The embryologist opens a small hole in the outer membrane of the embryo, known as the zona pellucid. The opening improves the ability of the embryo to leave its shell and implant into the uterine lining. Patients who benefit from assistant hatching include women with previous IVF failure, poor embryo growth rate, and older women. In some women, particularly older women, the membrane is hardened, making it difficult for the embryo to hatch and implant.
• Electric or vibratory stimulation to achieve ejaculation- ejaculation is acheived with electric or vibratory stimulation. This procedure is useful for men who cannot ejaculate normally, such as those with a spinal cord injury.
• Surgical sperm aspiration- the sperm is removed from part of the male reproductive tract, such as the vas deference, testicle or epididymis.

FUTURE TRENDS:
Letrozole and Aromatase Inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole (Femara). These drugs are used for treating breast cancer and are being investigated for stimulating ovulation in infertile women. Although letrozole is not approved for treatment of infertility, it has become widely used for this purpose in recent years. Progesterone is a hormone that is produced by the body during the menstrual cycle Progesterone drugs are sometimes given to women who have experienced frequent miscarriages. A progesterone drug may also be given after egg retrieval during an in vitro fertilization (IVF) cycle to help thicken the uterine lining (endometrium) so it can better hold the egg following implantation.Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulator (SERM). It is used to prevent breast cancer in high-risk women. It is also being studied in fertility treatments to induce ovulation. Tamoxifen works in a similar to clomiphene but may pose more health hazards, including a risk for blood clots and uterine cancer. Glucocorticoids are steroid hormones that are sometimes used in combination with IVF and intracytoplasmic sperm injection (ICSI) to help make the lining of the uterus more responsive to egg implantation. However, recent reviews caution that glucocorticoids do not help improve pregnancy success rates and should not be used routinely with assisted reproductive technologies.

CONCLUSION:
The review has successfully narrated all detail information regarding treatment of female infertility and prevention of recurrent abortions. The increased global warming, UV and cosmic rays, radiations of silicon medias, mobiles have generated the impairment of female infertility. Genetical disorder and hormonal imbalances are also can be rectified by drugs, alternatives medicines and physiotherapies. Hence there is effective treatment for female infertility.

REFERENCES:
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