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.
Showing posts with label Fertility Medications. Show all posts
Showing posts with label Fertility Medications. Show all posts
Thursday, November 15, 2007
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.
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.
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.
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.
Wednesday, November 7, 2007
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.
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.
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