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.

You don't get to see pictures like this very often

Trust

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.

Womb Raider

A UK High Court judge ruled earlier this year that the biological father of a child born to a surrogate should be able to keep the baby. The surrogate had been in a court battle over parenthood with the man following the birth of the child in December 2005. The court's decision was handed down in July, but only made public last week, after the Court of Appeal dismissed the
woman's appeal saying that the trial judge had 'crucially' found that the woman and her husband had deliberately embarked on a path of deception.
The woman, known only as 'Mrs P', had apparently deceived the man and his wife into believing that she had miscarried the child she had conceived using the commissioning father's sperm, and agreed to carry for them. Once the commissioning father found out that this was untrue, he and his wife launched legal proceedings. The judge found that while Mr and Mrs P had been good parents to the boy, they had deliberately embarked on surrogacy with the object of adding to their own family and had never intended to hand the baby over. The little boy now lives with his biological father and his wife, known only as Mr and Mrs J.
The court heard that the surrogate had also deceived another couple previously - in that case the father did not learn that a child had actually been born until the girl was four years old. Then, the girl's biological father, who had paid Mrs P £850, decided not to apply for custody of his daughter and Mrs P was allowed to keep her. The father instead sought a court order for contact with the girl, and later made an agreement with Mrs P that his daughter would be told about him at the appropriate time and that he would be allowed to see her.
The information about the deceptions came from the woman's 19-year old daughter, who informed the surrogacy agency that the couples had gone through. The surrogate already had three children of her own but was motivated by 'a compulsive desire to bear further children', found the court. The couple's actions were evidence of a 'desperate desire to parent
more children by fair means, or failing that, foul', said the judge. Mr Justice Coleridge, hearing the case at the High Court, ruled that the surrogate should give up the boy because she had set out to deceive both couples. It was for the court to decide, based on the best interests of the child, which set of parents would be better for the boy's upbringing in the long term, he added. Recognising that surrogacy arrangements are a feature of contemporary life, he acknowledged that 'when all goes according to plan they are a way of remedying the agony of childlessness'. But he added that 'when arrangements do not go according to plan, the result, in human terms and legal terms is, putting it simply, a mess' and that 'the cost, in terms
of appalling emotional pain for the parties, is huge'.The judge also issued a warning to surrogacy agencies, saying that they
should make more stringent background checks on women putting themselves forward to become surrogates. While surrogacy is legal in the UK, agencies must operate on a not-for-profit basis and surrogates are not allowed to be paid more than 'reasonable expenses'. Notwithstanding this, arrangements are unenforceable and usually if the surrogate changes her mind she will be entitled to keep the child.

Progesterone Supplementation

Progesterone is initially produced by the corpus luteum, a small structure formed on the ovary when the egg is released from the ovarian follicle. After about twelve weeks, the placenta begins to produce progesterone. Progesterone is vital to pregnancy support because it causes increased vascularization (greater blood flow) and thickening of the endometrium, which is the inner layer of the uterus. If pregnancy does not occur, progesterone levels fall triggering menstruation. Menstruation is essentially "shedding" of the endometrial lining of the uterus. These processes increase the ability of the endometrium to provide vital nutrients to the developing embryo.
Progesterone is responsible for the temperature rise that is measured by the basal body temperature chart. Progesterone is sometimes used to treat a "luteal phase defect". The luteal phase is the period between ovulation and menses. Insufficient production of progesterone by the corpus luteum might not provide adequate stimulation of the endometrium to support a pregnancy. An endometrial biopsy is often taken to document a luteal phase defect.
Progesterone is used in in vitro fertilization cycles to insure adequate development of the endometrium. The injectable form of progesterone(Gestone) provides the most predictable blood levels and is often used in IVF. It is administered by intramuscular injection and is painful. Some clinics are now using a gel form (Crinone) which is administered intravaginally or specially compounded suppositories may be prescribed.
In some women the ovaries do not make enough progesterone or the lining of the uterus does not respond well to normal amounts of progesterone. If this happens the lining of the uterus is not able to thicken or prepare for implantation of the fertilized egg. This may result in the failure of the fertilized egg to implant and pregnancy does not occur. There are many reasons why the ovaries might not produce enough progesterone. The different causes may be ovulation problems, endometriosis, fertility drugs, or "older eggs".
Progesterone supplementation is a medication that is taken after ovulation and it corrects the low progesterone hormone imbalance. The lining of the uterus responds to the progesterone medication, it thickens and prepares for the implantation and support of a pregnancy. A woman will continue to use progesterone until the placenta has developed and is able to support the pregnancy. (11-13 weeks after conception).
Progesterone supplementation can be given in the form of vaginal suppositories, injections (shots) or by mouth. The progesterone is usually started four days after you have had the shot that causes ovulation to occur (hCG or Profasi). You will continue the progesterone until you have had a negative pregnancy test or a normal menstrual period. If you conceive and are pregnant you will continue the medication for several weeks; the doctor will tell you when it is time to stop. Progesterone supplementation has few side effects. These may include breast tenderness, nausea, fatigue, or a 2-3 day delay in the start of your period.
The medication may be packaged with a patient information insert. The purpose of this insert is to provide information about progesterone to all patients taking it. The information in the insert pertains to all progesterone medication, both natural and synthetic. There is an increased risk of birth defects to babies exposed during pregnancy to synthetic progesterone. However, the progesterone supplementation prescribed by the physician is in a natural form and this does not increase the risks of birth defects. Please talk with your physician if you have any concerns.
Progesterone Suppositories are inserted into your vagina and are then absorbed by the body. You may notice some leakage of the medicine from your vagina when you are up and moving around. Do not worry about this because the medication is still being absorbed. You may want to wear a panty liner to protect your clothing. There are no activity restrictions while using the suppositories, including sex. It probably would be more comfortable to wait until after intercourse before inserting the suppository. Occasionally the leakage of the medicine can be irritating to the skin around your vagina; contact your physician if the vaginal irritation becomes too bothersome.Progesterone Oral Medication comes in several different forms that are taken by mouth. Progesterone Injections are "shots" that are injected into your muscle (usually the buttocks or thigh) and the progesterone is absorbed by your body. You may notice soreness or tenderness at the injection site while you are taking the progesterone shots. After an injection you may apply an ice-pack to the area for relief. Please contact your physician if the injections become too painful.
Progesterone has many other uses not related to infertility treatment some of which have dubious scientific support.A qualified physician should be personally consulted prior to the administration of any hormone product.

Letrozole for Ovulation Induction

Ovulatory dysfunction is one of the most common causes of reproductive failure in subfertile and infertile couples. Since the first clinical trial was published in 1961, clomiphene citrate (CC) has been the front-line therapy for ovulation induction. Its use quickly expanded to other empiric indications, such as luteal phase defect and the enhancement of fecundity in unexplained infertility. Failure to respond to CC occurs in up to 20% of cases, which may then require the use of injectable gonadotropins. The drawbacks of this approach are its high cost (both for the medication and the extensive monitoring it requires), risk of the potentially life-threatening ovarian hyperstimulation syndrome (OHSS), and, perhaps most importantly, the significant risk of high-order multiple gestations. Clearly, an inexpensive yet equally efficacious oral alternative would be ideal. Recent research has focused on the successful use of aromatase inhibitors, mainly letrozole, for ovulation induction. The Rotunda medical team have begun incorporating letrozole into treatment plans for appropriately selected patients.

CC is an estrogen-receptor (ER) modulator. It binds to nuclear ER in the hypothalamus, mitigating the usual negative feedback of estrogen on GnRH during the follicular phase. This results in augmented FSH stimulation to the ovary from the pituitary as a result of changes in GnRH pulsatility and is the mechanism for ovulation induction or enhancement. Unfortunately, CC can bind nuclear ER for an extended period of time (6-8 weeks) and eventually depletes ER in other estrogen-dependent tissues, such as the endometrium and cervix. This leads to diminished endometrial development and decreased cervical mucus production. When used in the early follicular phase, letrozole inhibits estrogen synthesis, thereby causing enhanced GnRH pulsatility and consequent FSH and inhibin stimulation. This results in normal or enhanced follicular recruitment without the risk of multiple ovulation and OHSS. Letrozole has a very short half-life (~45 hours) and, therefore, is quickly cleared from the body. For this reason, it is less likely to adversely affect the endometrium and cervical mucus.

Letrozole has also been shown to improve outcome in cycles combining injectable FSH with oral ovulation induction. Recent studies report that the combination of letrozole and FSH enhances follicular recruitment while reducing the amount of FSH needed for optimal stimulation, ultimately reducing the cost of the cycle. This approach has also been useful in patients who previously responded poorly to superovulation treatment protocols.

The usual dose for letrozole ovulation induction is 2.5 mg on cycle days 3-7. Ongoing research using a single dose (10-30mg) on cycle day 3 shows similar rates of ovarian stimulation. Single doses as high as 60 mg have been administered without negative effects. Potential side effects of estrogen depletion, including hot flashes, nausea, and vomiting, have been reported in older breast cancer patients who were given the medication on a daily basis for several months. When used in a healthy population for a short time, the medication is much more tolerable. The pregnancy outcomes for letrozole ovulation induction have been very encouraging. The results of several studies show that letrozole and letrozole + FSH cycles had the highest pregnancy rates of studied regimens, and that letrozole cycles had the lowest multiple gestation rate.

Research into the role of aromatase inhibitors in fertility treatment is ongoing. As with any new course of treatment, it will be important to study long-term effects on the patient, the pregnancy and the conceived children. Due to their short half-life, it is unlikely that letrozole or other aromatase-inhibitors will be associated with any significant negative effects.