Thursday, November 15, 2007

Human chorionic gonadotropin

Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the syncytiotrophoblast (part of the placenta). Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG. Because hCG is produced also by some kinds of tumor, hCG is an important tumor marker, but it is not known whether this production is a contributing cause or an effect of tumorigenesis.
Its primary role is to support the corpus luteum which secretes estrogen and progesterone. These hormones are necessary to support a pregnancy during the first trimester. hCG levels rise when pregnancy is established and it is the hormone measured by pregnancy urine test kits.

hCG products such as Profasi and Pregnyl are derived from human tissue. Ovidrel is a new pure product that is derived from mammalian cell DNA technology. It is injected subcutaneously facilitating patient administration. hCG is extensively used as a parenteral fertility medication in lieu of luteinizing hormone. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of hCG. As ovulation will happen about 40-45 hours after the injection of hCG, procedures can be scheduled to take advantage of this time sequence. Thus, patients who undergo IVF, typically receive hCG to trigger the ovulation process, but have their eggs retrieved at about 36 hours after injection, a few hours before the eggs actually would be released from the ovary. In a normal menstrual cycle, the release of LH is triggered when hormones (such as estrogen) reach the appropriate levels. This is governed by hormonal relationships mediated though the hypothalamic-adrenal-pituitary axis. As hCG supports the corpus luteum, administration of hCG is used in certain circumstances to enhance the production of progesterone.

In the male, hCG injections are used to stimulate the leydig cells to synthesize testosterone. The intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. Typical uses for hCG in men include hypogonadism and fertility treatment. In the world of performance enhancing drugs, hCG is increasingly used in combination with various anabolic androgenic steroid (AAS) cycles. When AAS are put into a male body, the body's natural negative feedback loops cause the body to shut down its own production of testosterone via shutdown of the HPTA (hypothalamic-pituitary-testicular axis). High levels of AASs that mimic the body's natural testosterone trigger the hypothalamus to shut down its production of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Without GnRH the pituitary gland stops releasing luteinizing hormone (LH). LH normally travels from the pituitary via the blood stream to the testes where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone, causing testicular atrophy. In males, hCG mimics LH and helps restore / maintain testosterone production in the testes. As such, hCG is commonly used during and after steroid cycles to maintain and restore testicular size as well as endogenous testosterone production. However, if hCG is used for too long and in too high a dose, the resulting rise in natural testosterone will eventually inhibit its own production via negative feedback on the hypothalamus and pituitary.

During first few months of pregnancy, the transmission of HIV-1 from woman to fetus is extremely rare. It has been suggested this is due to the high concentration of hCG, and that the beta-subunit of this protein is active against HIV-1.

Wednesday, November 14, 2007

Follicle Stimulating Hormone (FSH)

Follicle stimulating hormone (FSH) is naturally produced by the pituitary gland and stimulates the recruitment and development of the ovarian follicles located on the ovaries, each of which contains an egg. FSH is also referred to as a pituitary gonadotropin. The production of FSH and other reproductive hormones is controlled by the complex interaction of several hormones in a biologic feedback system known as the "hypothalamic-pituitary-adrenal" axis. The hypothalamus is the "master gland" in control of regulating these processes.

The first FSH containing commercial gonadotropin in India, Pergonal, was released by Serono Laboratories. Pergonal is derived from the urine of post-menopausal women and purified for injection. FSH levels are higher in women who are menopausal making their urine a good source for extraction. Pergonal also contains leutinizing hormone (LH) which produces many effects including higher estrogen levels.Newer FSH products include Gonal-F and Recagon which are obtained from mammalian cell cultures through recombinant DNA technology. These products are pure and do not contain the "contaminants" seen in Pergonal. Pergonal has to be administered by intramuscular injection while the newer medications are given subcutaneously with much less discomfort Both human and genetically derived products are difficult to obtain and manufacture and are therefore expensive.

Opinions differ as to the need for additional LH in FSH stimulated cycles. Some physicians prefer protocols that combine products containing LH with Gonal-F (pure FSH). When a patient is "down regulated" with Lupride, or especially Ovurelix, natural levels of LH are reduced to very low levels and some externally administered LH is believed by many to be beneficial.
Egg quality is difficult (at best) to judge but some embryologists believe pure FSH cycles produce "better quality" eggs.

In procedures such as in vitro fertilization, FSH is administered by injection to cause the development of numerous eggs which can be retrieved and fertilized. When FSH is used in stimulated intrauterine insemination cycles, there is less control over how many eggs are ovulated thus increasing the chances of multiple births. Most cases of quadruplets, or more, result from stimulated IUI cycles. Patients must be closely monitored by a Fertility Physician to minimize the risk of multiple births.

FSH should only be administered by a Fertility Physician thoroughly trained in its use. Serious side effects can occur and patients must be closely monitored with estradiol hormone level measurements and ultrasound. Hyperstimulation is a very serious, but rare, complication that can result in stroke and other like threatening events. Side effects are minimized when these products are monitored by specialists with extensive clinical training in their use.

Tuesday, November 13, 2007

Medications for Down Regulation

Lupride and Ovurelix are fertility drugs that "down regulate" reproductive hormone production causing a reduction in levels of follicle stimulating hormone, luteinizing hormone, and estrogen. Lupride and Ovurelix both cause these effects, however, by different physiologic mechanisms.

Lupride is widely used for the treatment of endometriosis and was the first "down regulator" used in in vitro fertilization cycles. Endometrial cells are dependent upon estrogen for growth and Lupride dramatically lowers estrogen levels. Unfortunately, this lowering is accompanied by the same side effects as menopause. Lupride and Ovurelix are administered according to specific protocols in IVF to prevent premature ovulation, and in some cases to exacerbate the response to follicle stimulating hormone (flare protocol).

Lupride is a GnRH agonist which works at the hypothalamus (a small gland located at the base of the brain ) whereas Ovurelix is a GnRH antagonist which completely blocks the effect of gonadotropin releasing hormone at the pituitary gland thus creating a "more complete "down regulation". IVF cycles are precisely timed to insure that the follicles are optimally developed at the time of retrieval. FSH is administered and dosages are adjusted based upon periodic ultrasound scans and estradiol measurements. In a "normal" or "non-stimulated" cycle, luteinizing hormone surges to signal ovulation. If this occurs too soon in an IVF cycle, ovulation could be triggered before the eggs are mature and the cycle could be lost. The LH surge cannot occur while Lupride or Ovurelix are administered and thus premature ovulation is prevented. Once the follicles are mature, an injection of hCG is given 36-38 hours prior to retrieval to signal ovulation. The body responds to hCG in the same manner as it does to LH.

Many infertility clinics choose to use Lupride or Ovurelix because the down regulation is more complete and the dosing regimen is easier. Lupride is started 7 days before the next expected menses and Ovurelix is started after 4 to 6 days of FSH/hMG stimulation. Doses vary dependent upon patient specific protocols.

Monday, November 12, 2007

Clomiphene Citrate

Clomiphene Citrate was one of the first infertility medications and is widely employed to induce ovulation. Originally, it was thought that it might hold potential as a birth control agent but research revealed its ovulation inducing properties.
Clomiphene Citrate works at the hypothalamus (a small organ located at the base of the brain) to cause the release of gonadotropin releasing hormone (GnRH) into the bloodstream. GnRH travels to the pituitary gland where it stimulates the release of follicle stimulating hormone (FSH). FSH stimulates the recruitment and development of eggs within the ovarian follicles. Clomiphene Citrate therapy should not be administered for more than 3- 6 months dependent upon many individual patient variables. Clomiphene Citrate studies have clearly demonstrated that pregnancy is most likely to occur during the first three months of therapy. There is little advantage to increasing the clomiphene dosage beyond that required to regulate ovulation.

Even though ovulatory dysfunction is present, a male semen analysis should be performed. Male factor is a contributor in over 47% of infertility cases and must be ruled out prior to treatment of the female. Clomiphene Citrate therapy is often administered by the non-specialist; however, it is not always the best choice and can produce unwanted side effects. Fertility physicians are trained to diagnose the various complex conditions that can cause ovulatory disorders, such as polycystic ovarian syndrome. There are also other alternatives to Clomiphene Citrate, especially in the PCOS patient where Metformin often is the drug of first choice. Clomiphene Citrate should not be administered to women over the age of 35 without a complete fertility evaluation. Fertility can decline rapidly in older female age groups. Once again, Clomiphene Citrate should not be prescribed without a male semen analysis.

Clomiphene Citrate is the most used and abused medication for infertility treatment. It was introduced to the clinical market in 1967 and almost immediately replaced the surgical procedure - wedge resection of the ovaries - for primary treatment of anovulation in patients with polycystic ovarian disease (PCOD). Clomiphene Citrate is still widely used by gynecologists for that purpose and others. It is important to remember that proper use of the medication will usually yield gratifying results while expanding its use to lesser indications may be counterproductive and often results in unsuccessful outcomes. Clomiphene Citrate's best and most common indication is for induction of ovulation in euestrogenic, normoprolactinemic, and anovulatory patients. The majority of these patients will have PCOD, which is a clinical diagnosis of chronic anovulation with symptoms and signs of Hyperandrogenism. The definition implies that there is adequate endogenous estrogen production and that hyperprolactinemia has been excluded. Patients with hypoestrogenic anovulation are not good candidates for Clomiphene Citrate as it works as an antiestrogen at the hypothalamus level.

Examples of patients with hypoestrogenism are those with premature ovarian failure, exercise-related amenorrhea, and low body weight with anorexia. Clomiphene Citrate does not work well in patients who are overweight. The second indication for clomiphene use is for the purpose of superovulation, in ovulating patients, in conjunction with assisted reproduction such as intrauterine insemination (IUI) or in-vitro fertilization (IVF). Clomiphene Citrate may also be used to treat patients with luteal phase defects in conjunction with progesterone supplementation in the luteal phase. The wide use of Clomiphene Citrate to treat patients with unexplained infertility can be counterproductive as Clomiphene Citrate can have adverse effects on the cervical mucus and on implantation at the endometrial level.

Clomiphene Citrate can be considered in young patients (< 30 years) but certainly for no longer than three cycles and with proper monitoring. Clomiphene Citrate is started at a dose of 50 mg / day for 5 days in anovulatory patients. It is important to remember that these patients do not have cycles and the conventional "cycle day 5 - 9" should not be used. Rather, the first day of clomiphene use can be conveniently called day 1 of the cycle. Patients should look for ovulation, wither by a BBT chart or using follicular studies, 7 to 10 days after the last clomiphene pill or on days 12 - 15 of the clomiphene cycle (first day of Clomiphene Citrate is day 1).

Clomiphene Citrate in some thin patients dosed at 25 mg / day for five days can be adequate. A post coital test can be performed in the first cycle of clomiphene use to check for adequate mucus production. If patients ovulate on the 50 mg clomiphene dose, they should be kept on it for 3 - 4 months before re-evaluation. If patients do not ovulate on the lower dosage,clomiphene should be increased in increments of 50 mg / day for subsequent cycles. It is important to remember that 70 -80% of patients who will respond to Clomiphene Citrate will ovulate on the 50 - 100 mg dosage and of those who get pregnant 80 - 90% will do so within 3 - 4 ovulatory cycles.

When clomiphene fails, it is extremely important to distinguish between ovulation and conception failure. Clomiphene Citrate Ovulation Failure is arbitrary defined as failure to ovulate on doses of 150 mg / day for 5 days (even though 10 - 20% of patients can ovulate on higher dosages, it is important to re-evaluate the patient at this stage)

What are our options to induce ovulation for these patients?
a)Clomid doses can be increased to a maximum of 250 mg / day for five days or consider increasing the duration (100 mg / day for 8 days).

b) Clomid does not work well in extremely obese patients (> 90 Kgs or BMI > 30).These patients usually have insulin resistance and those patients should be highly encouraged to lose weight before induction of ovulation. Insulin sensitizing agents such as Metformin (Glucomet) or Hyponidd should be the primary treatment. Metformin can be started at the dose of 850 mg / day for one or two weeks, increased to 1700 mg p.o., for the next week, and maintained at the same dose thereafter.

Friday, November 9, 2007

Diwali

The word "Diwali" is derived from the Sanskrit word "Deepavali" - Deepa meaning light and Avali, meaning a row. It means a row of lights and indeed illumination forms its main attraction. Every home - lowly or mightly - the hut of the poor or the mansion of the rich - is alit with the orange glow of twinkling diyas-small earthen lamps - to welcome Lakshmi, Goddess of wealth and prosperity. Multi-coloured Rangoli designs, floral decorations and fireworks lend picturesness and grandeur to this festival which heralds joy, mirth and happiness in the ensuring year. Diwali is also known as the Festival of Lights. Light is significant in Hinduism because it signifies goodness. So, during the Festival of Lights, 'deeps', or oil lamps, are burned throughout the day and into the night to ward off darkness and evil. Homes are filled with these oil lamps, candles and lights. Diwali is celebrated on the last day of the last month of lunar calendar. This year it begins on October 21st and ends on October 25th. This weeklong festival is a tradition in every Hindu household around the world. It is the beginning of the New Year (2051), a start to a new fiscal year and a brand new beginning for all. Diwali is celebrated for five days, each day having it's own significance and ritual. Many legends and myths are also attached to each day. Each region of India celebrates Diwali in it's own unique way.
In northern India, especially in places like the Punjab, Diwali is dedicated to the worship of Lord Rama, who had been exiled from his empire, India, for 14 years. During that time Lord Rama fought and won tenuous struggles in the south part of the Indian sub-continent (what is now Sri Lanka). Diwali marks his victorious return to his kingdom. While in Bengal, Kali/Durga, the goddess of strength, is worshipped. This reverence is called "Kali Chaudas or Kal Chaturdasi". Strength is a positive attribute for one to have but it must be used to protect others from harm and used only in good and pure deeds. Also during Diwali, the goddess of wealth, Lord Lakshmi is worshipped. This practice is called "Dhanteras". It is believed that he or she who worships Lord Lakshmi during Diwali is bestowed wealth and prosperity. In Hindu society and culture, wealth is seen as a positive notion. It is not a corruptive contrivance used to harm others. What is corrupt is one's attitude towards wealth. Wealth equals power and power is good, as long as it does not harm another living creature. Wealth should be used in pure and good activities, not leading anyone down a path of destruction. Another practice during Diwali is "Bhai Dooj" or "Bhai Beej". On this day, women are given gifts from their brothers and held in the highest respect. The myth behind this begins when Bhagawaan Mahavir found nirvana, his brother Raja Nandivardhan was distressed because he missed him and was comforted by his sister Sudarshana. Since then, women have been revered during this festival.
Each of the five days in the festival of Diwali is marked with a significant worship or 'puja' of a certain deity that differs throughout India. Each is also separated by a different tradition. But what remains the same throughout is that this day is a celebration of life, joy and goodness. From darkness we enter into light, and light empowers us to do good deeds and bring us closer to divinity.
Diwali is the festival of Laxmi, the Goddess of prosperity and wealth. It is believed that Goddess Laxmi visit everyone during Diwali and brings peace and prosperity to all. On the night of diwali "Lakshmi-Pujan" is performed in the evenings. A traditional Puja is performed after sunset in all the homes. Five pieces of ghee diyas (lamps) are lit in front of the deities, Naivedya of traditional sweets is offered to the Goddess and devotional songs- in praise of Goddess Laxmi are sung.
After the Puja people light diyas (lamps) in their homes to usher in light, and clear the darkness from the world. In villages cattle's are adorned and worshipped by farmers as they form the main source of their income. In south cows are offered special veneration as they are supposed to be the incarnation of Goddess Lakshmi and therefore they are adorned and worshipped on this day.

Diwali or more aptly Deepavali is very enthusiastically celebrated for five continuous days and each day has its significance with a number of myths, legends and beliefs.

First Day : DHANTERAS or DHANTRAYODASHI.
It is the thirteenth day of the month of Ashwin. The word "Dhan" means wealth. As such this day of the five-day Diwali festival has a great importance for the rich mercantile community of Western India. Houses and Business premises are renovated and decorated. Entrances are made colourful with lovely traditional motifs of Rangoli designs to welcome the Goddess of wealth and prosperity. To indicate her long-awaited arrival, small footprints are drawn with rice flour and vermilion powder all over the houses. Lamps are kept burning all through the nights. Believing this day to be auspicious women purchase some gold or silver or at least one or two new utensils. "Lakshmi-Puja" is performed in the evenings when tiny diyas of clay are lighted to drive away the shadows of evil spirits. "Bhajans"-devotional songs- in praise of Goddess Laxmi are sung and "Naivedya" of traditional sweets is offered to the Goddess. There is a peculiar custom in Maharashtra to lightly pound dry coriander seeds with jaggery and offer as Naivedya. In villages cattles are adorned and worshipped by farmers as they form the main source of their income. In south cows are offered special veneration as they are supposed to be the incarnation of Goddess Lakshmi and therefore they are adorned and worshipped on this day.
A very interesting story about this day is of the sixteen year old son of King Hima. As per his horoscope he was doomed to die by a snake-bite on the fourth day of his marriage. On that particular fourth day of his marriage his young wife did not allow him to sleep. She laid all the ornaments and lots of gold and silver coins in a big heap at the entrance of her husband's boudoir and lighted innumerable lamps all over the place. And she went on telling stories and singing songs. When Yam, the god of Death arrived there in the guise of a Serpent his eyes got blinded by that dazzle of those brilliant lights and he could not enter the Prince's chamber. So he climbed on top of the heap of the ornaments and coins and sat there whole night listening to the melodious songs. In the morning he quietly went away. Thus the young wife saved her husband from the clutches of death. Since then this day of Dhanteras came to be known as the day of "YAMADEEPDAAN" and lamps are kept burning throughout the night in reverential adoration to Yam, the god of Death.
The SECOND day is called NARAK-CHATURDASHI or CHOTI DIWALI.
IT is about 'Narakasur Vadh' (killing of the demon Narakasur), and is held on the fourteenth day of the month of Aashwin. The story goes that the demon king Narakasur ruler of Pragjyotishpur ( a province to the South of Nepal) after defeating Lord Indra had snatched away the magnificent earrings of Aditi, the Mother Goddess and imprisoned sixteen thousand daughters of the gods and saints in his harem. On the day previous to Narakachaturdashi, Lord Krishna killed the demon and liberated the imprisoned damsels and also recovered those precious earrings of Aditi. As a symbol of that victory Lord Krishna smeared his forehead with the demon king's blood. Krishna returned home in the very early morning of the Narakachaturdashi day. The womenfolk massaged scented oil to his body and gave him a good bath to wash away the filth from his body. Since then the custom of taking bath before sunrise on this day has become a traditional practice specially in Maharashtra. In South India that victory of the divine over the mundane is celebrated in a very peculiar way. People wake up before sunrise prepare blood by mixing Kumkum in oil and after breaking a bitter fruit that represents the head of the demon King that was smashed by Krishna, apply that mixture on their foreheads. Then they have an oil bath using sandalwood paste. In Maharashtra also, traditional early baths with oil and "Uptan" (paste) of gram flour and fragrant powders are a `must'. All through the ritual of baths, deafening sounds of crackers and fireworks are there in order that the children enjoy bathing. Afterwards steamed vermiceli with milk and sugar or puffed rice with curd is served.
The THIRD day : Diwali
On the dark new moon night, the entrances to all homes are lit up and decorated with rangoli patterns to welcome Lakshmi, the radiant consort of Vishnu and the goddess of wealth and lustre. Lakshmi Puja is performed on this day. Diwali is the last day of financial year in traditional Hindu business and businessmen perform Chopda Pujan on this day on the new books of accounts. The day ends with a mega cracker bursting sessions. For 5-6 hours, every family burns fire crackers worth thousands of ruppees. Poplular fire crackers are sparkling pots, bombs, rockets etc.
The FOURTH day : New Year day or Bestavarsh
The day after the Lakshmi Puja, most families celebrate the new year by dressing in new clothes, wearing jewellery and visiting family members and business colleagues to give them sweets, dry fruits and gifts. Among the business communities of Gujarat, Rajasthan, Madhya Pradesh and Maharashtra, Diwali is the festival when the new business year begins. All business establishments and families perform muharat pujan or veneration of their books. Stock brokers do mahurat trading or symbolic auspicious business deals to Diwali. Diwali, one of the longest festivals in the Hindu year, is a time when everything in India comes to a standstill except family life, feasting and shopping. Diwali is considered auspicious for shopping, inaugurations of new homes, business deals or for starting any new ventures and projects.
The Fifth day of Diwali : Bhai Dhooj
The second day of the bright forthnight (Shukla Paksh) of Kartik is called "Bhaiya-Duj". It comes once a year - after Diwali. The name itself denotes the day of the festival i.e.Diwali falls on the absolutely dark night of Amavasya (new moon), Dooj comes two days after Diwali. Many years ago, in the Vedic era, Yama (Yamraj, the Lord of death) visited His sister Yamuna(Yami) and she put the auspicious tilak on his forehead, they ate talked and enjoyed together and exchanged special gifts as a token of their love for each other and Yamraj announced that anyone who receives tilak from his sister on this day will never be thrown. Since then it became imperative for the brother to go to his sister's house to celebrate Bhaiyaduj.On Bhai Dooj, the teeka is applied on the brother's forehead. It is a day dedicated to sisters. We have heard about Raksha Bandhan (brothers day). Well this is sisters day. The sister usually goes in the morning and does the puja in the mother's house, before the brothers leave for their places of study or work.
Enjoy your Diwali & Have a rocking Weekend.