The British Fertility Society has issued new guidelines for the treatment of women with fertility problems that help doctors address the impact of obesity.
"Obesity reduces the chances that a woman will conceive naturally and decreases the possibility that fertility treatment will be successful," said Tony Rutherford, Chair of the BFS's Policy and Practice Committee.
The new guidelines recommend that clinicians inform their patients about the negative effects of extra weight on the chances of conceiving naturally. They also suggest that clinicians defer the provision of fertility treatment to women whose body mass index (BMI) is greater than 35 kg/m2.
Women younger than 37 years should be encouraged to reduce their BMI to less than 30 kg/m2 to maximize the effectiveness of fertility treatment and to reduce the associated risks associated with fertility treatment, the guidelines state.
They add that women should be assisted in this, with the provision of psychologic support, dietary advice, exercise classes and, where appropriate, weight-reducing agents or bariatric surgery.
"The BFS has produced these new guidelines to help doctors provide safer and more effective fertility treatment for women," said Rutherford.
"We want to work with our patients to improve their chances of becoming pregnant with minimum risk to their health and that of their child."
Friday, November 16, 2007
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.
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.
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.
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.
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.
Sunday, November 11, 2007
Saturday, November 10, 2007
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