The Ramblings of a Middle Aged Fertility Physician whose life revolves around Eggs, Sperms & Embryos....
Sunday, November 4, 2007
Acupuncture Bad For IVF Success
Contrary to the widely held belief that acupuncture enhances a woman's chances of successfully becoming pregnant whilst undergoing IVF treatment, a study at the University of Oklahoma found that women who combine acupuncture and IVF were 37 per cent less likely to conceive than those who underwent IVF treatment alone. The new findings caused head researcher Dr LaTasha Craig, to warn that acupuncture should not be recommended until further research has been conducted to resolve the discrepancy between this study and earlier research. Previous studies had appeared to indicate a marginal increase in IVF efficacy or showed no obvious benefit, allowing some to scientifically postulate that the ancient far eastern medical practice of acupuncture might somehow affect certain muscles and glands of the nervous system to help the
lining of the uterus become more receptive to embryo implantation.
The latest study evaluated the results of 97 patients with an average age of 35 who were randomly divided into two groups. One group received acupuncture for 25 minutes before and after embryo implantation. The pregnancy rate for the IVF group without acupuncture was 69.9 per cent compared to the 43.8 per cent less successful pregnancy rate for those who
received the two-pronged acupuncture 'therapy' approach. Dr Craig suggested that other factors may have counteracted any therapeutic effect of acupuncture such as the stress from undergoing acupuncture just before IVF or from travel in traffic to external acupuncture clinics and onto IVF appointments.
Some clinics regularly offer acupuncture with its IVF services, according to Mark Bovey from the British Acupuncture Council, who was alarmed by the results. Although the number of women who undergo IVF alongside acupuncture procedures has skyrocketed, many doctors believe that the placebo effect is a likely explanation for any perceived benefit.
Saturday, November 3, 2007
Fertility Injections - A Waste of Time?
New research found that hormone injections to achieve pregnancy do not 'provide any added benefit' financially or medically in women under 40 as an alternative infertility treatment before advancing to IVF, announced head researcher Dr Richard Reindollar, from the Dartmouth-Hitchcock Medical Centre in New Hampshire, last week at the annual meeting of the American Society for Reproductive Medicine in Washington last week. The comprehensive study indicates that the thousands of Indian women each year who receive follicle-stimulating hormone (FSH) injections costing Rs 20,000 - Rs 25,000 per course for infertility treatment before resorting to IVF treatment may actually be prolonging the time it takes to become pregnant at unnecessarily increased costs and health risks than if they were to undergo IVF treatment straight away.
In the study of 503 infertile couples, those who were 'fast-tracked' to IVF treatment became pregnant three months earlier than those couples who underwent the daily injections together with artificial insemination (IUI) before, if unsuccessful, undergoing IVF treatment, which also involves ovary-stimulating injections but is coupled with the more invasive egg
extraction and embryo implantation procedures. In practice, women typically begin treatment by trying clomiphene pills together with IUI and when that is unsuccessful most Indian and many UK clinics then offer a course of injections with IUI before performing IVF as a final treatment stage. Both groups were initially unsuccessful with pills and IUI and both had a similar chance of becoming pregnant. Ultimately 78 per cent of those fast-tracked and 75 per cent of those receiving injections were successful but the fast-tracked couples had a 40 per cent increased chance to become pregnant
within the first eight months versus eleven months of treatment, and saved overall costs by an average of £5,000- reducing average payment from £35,700 to £30,750.
Women may also be placing themselves at prolonged health risk. The injections stimulate the ovaries egg production and have significant physical side-effects including headaches, abdominal pain and ovarian hyperstimulation syndrome, which in extremely rare cases can be fatal. They also increase the risk of multiple births by 20 to 30 per cent, which in turn increases the risk of birth defects and pregnancy-induced hypertension. Contrary to National Institute for Health and Clinical Excellence guidance, which recommends the NHS pay for hormone injections only for women with endometriosis, many private clinics offer them more generally often in cases of unexplained infertility, according to Mark Hamilton, chairman of
the British Fertility Society. Infertility affects one in seven British couples and Hamilton urges patients to carefully consider with their doctors the efficacy of infertility treatments before attempting treatments with lower success levels. Bill Ledger, Professor of Obstetrics and Gynaecology at the University of Sheffield felt this study adds to mounting evidence in
support of the cost-saving elimination of injections and redirection of those funds into providing cheaper IVF treatment with an equal success rate without the delay.
In the study of 503 infertile couples, those who were 'fast-tracked' to IVF treatment became pregnant three months earlier than those couples who underwent the daily injections together with artificial insemination (IUI) before, if unsuccessful, undergoing IVF treatment, which also involves ovary-stimulating injections but is coupled with the more invasive egg
extraction and embryo implantation procedures. In practice, women typically begin treatment by trying clomiphene pills together with IUI and when that is unsuccessful most Indian and many UK clinics then offer a course of injections with IUI before performing IVF as a final treatment stage. Both groups were initially unsuccessful with pills and IUI and both had a similar chance of becoming pregnant. Ultimately 78 per cent of those fast-tracked and 75 per cent of those receiving injections were successful but the fast-tracked couples had a 40 per cent increased chance to become pregnant
within the first eight months versus eleven months of treatment, and saved overall costs by an average of £5,000- reducing average payment from £35,700 to £30,750.
Women may also be placing themselves at prolonged health risk. The injections stimulate the ovaries egg production and have significant physical side-effects including headaches, abdominal pain and ovarian hyperstimulation syndrome, which in extremely rare cases can be fatal. They also increase the risk of multiple births by 20 to 30 per cent, which in turn increases the risk of birth defects and pregnancy-induced hypertension. Contrary to National Institute for Health and Clinical Excellence guidance, which recommends the NHS pay for hormone injections only for women with endometriosis, many private clinics offer them more generally often in cases of unexplained infertility, according to Mark Hamilton, chairman of
the British Fertility Society. Infertility affects one in seven British couples and Hamilton urges patients to carefully consider with their doctors the efficacy of infertility treatments before attempting treatments with lower success levels. Bill Ledger, Professor of Obstetrics and Gynaecology at the University of Sheffield felt this study adds to mounting evidence in
support of the cost-saving elimination of injections and redirection of those funds into providing cheaper IVF treatment with an equal success rate without the delay.
Friday, November 2, 2007
Investigating The Infertile Male
It is natural for the attention of the gynecologist and family practitioner to initially turn toward the female in cases of infertility. Although infertility is generally viewed a ‘female problem’, fully 45% of infertile couples have male infertility as a contributing cause. It makes sense then to begin the fertility evaluation with a basic evaluation of the male partner. Because significant male factor infertility is generally treated with in vitro fertilization, needless hysterosalpingograms, laparoscopies and clomiphene cycles can be avoided by early detection of significant dysfunction in the male partner. The savings of time and money can be tremendous. IVF with intracytoplasmic sperm injection (IVF/ICSI) has made it possible to successfully treat virtually all cases of male infertility, even with only a few moving sperm in the entire ejaculate.
The evaluation of the male partner starts with a competent semen analysis. Non-specialized laboratories, such as Ranbaxy and Metropolis, perform a World Health Organization (WHO) semen analysis. This is a crude screening test and should be replaced by the strict semen analysis (Kruger) that is done by most fertility centers. The difference between the WHO and the Kruger test is that, with the Kruger test, sperm morphology is evaluated in a very stringent manner. The results of the Kruger test predict fertilization rates in vitro and presumably in vivo as well. The WHO does not predict outcome and will frequently miss subtle but clinically significant sperm abnormalities. The cost of the Kruger test is the same or less than a WHO analysis at our center.
When male infertility is suspected and tests reveal abnormal semen parameters, the couple should be referred to a fertility physician and/or urologist for further evaluation. Conditions warranting referral for male infertility are: a sperm concentration of less than 20 million per mL, motility less than 35%, and morphology less than 5% (Kruger) or 30% (WHO).
A direct antisperm antibody test should be done in cases where the male has a history of genital trauma, genital surgery or has never initiated a pregnancy. The direct antibody test is done on a semen sample and detects whether antibodies are attached to the sperm themselves. The cutoff for a positive test varies between labs but is usually considered positive when greater than 10%-20% of sperm are bound. Couples with antisperm antibodies should be referred to a fertility physician for further evaluation and treatment.
Genetic evaluation of male infertility is indicated when there is a sperm concentration less that 5 million per milliliter. This male infertility evaluation should consist of a karyotype and a study to look for microdeletions on the long arm of the Y chromosome (Yq deletion study). An assay for DNA fragmentation in the sperm cells may also be helpful in select patients. If azoospermia is present, carrier status for one of the cystic fibrosis mutations should be ruled out. These men should, of course, be referred for a urological evaluation. If surgical treatment of the infertile male is not indicated, a fertility physician can then complete treatment.
Hormonal evaluation of the infertile male is indicated when there is a history of sexual dysfunction, azoospermia or abnormal physical findings. This workup, which consists of testosterone, FSH, LH and prolactin levels, should be accompanied by urological consultation.
Thursday, November 1, 2007
Triple Marker Test
The multiple marker test (sometimes referred to as the triple screen) can tell you if your baby is at an increased risk of having certain birth defects and genetic abnormalities. If you choose to have this test, it's important to understand that a "positive" or abnormal result doesn't necessarily mean that your baby has a problem. Infact, only about 10 percent of women with abnormal results have babies with birth defects. In general, an abnormal result means only that you may need further testing, such as ultrasound or amniocentesis, to know for sure. On the other hand, a negative or normal result is not a guarantee that your baby is healthy - but it does mean that your baby's chances of having certain birth defects are much lower. And that's why a lot of women opt to take it. Current research indicates that this test will detect 75 to 80 percent of neural tube defects (such as spina bifida and anencephaly) and 60 percent of Down syndrome in babies of women younger than 35, and 75 percent of neural tube defects and Down syndrome in babies of women 35 and older. Only about 3 to 5 percent of women will receive a positive (abnormal) result on the multiple marker - and on an average, only about 10 percent of those women will actually have a baby with a problem. That adds up to a lot of false positive results. Statistics from one of the companies that offers a multiple marker test show an even higher rate of false positives. If 1000 pregnant women take this test, only about 25 of them will show an increased risk for a baby with neural tube defects, and of those, only one or two will actually have a baby with Down syndrome. On the other hand, some women whose test results are normal will have a baby with one of these problems.
The multiple marker test measures your blood levels of three substances: alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3). For years, women were screened for AFP alone in a test called the maternal serum AFP or MSAFP, but now most labs check for all three substances because they can tell more that way. Some hospitals screen for the hormone inhibin A as well, in what's called a quadruple screen test. When this compound is added to the test, the detection rate for Down syndrome increases to between 67 and 76 percent in women younger than 35. It's usually done between 15 and 20 weeks of pregnancy, with 16 to 18 weeks (when the hormone levels are the most consistent) being the optimum time. You'll have a blood sample taken and sent to a lab for analysis. The lab analyzes the levels of AFP, hCG and uE3 (and sometimes inhibin A) in your blood and determines whether they fall within a "normal" range for this stage of your pregnancy, based on your age, weight, race, and other factors (such as having diabetes). Having too much or too little of these substances in your blood is considered a positive, or abnormal, result. Results are generally available in one or two weeks. Your level of AFP and the other substances are considered individually and in combination to determine whether you and your baby are at risk for certain problems. The results tell you what your baby's chances are of having each kind of birth defect. For example, on average, a 35-year-old woman has a 1 in 250 to 270 chance of having a baby with Down syndrome. If the results show that your chances of having a baby with any of the defects tested for are higher than average for your age, you'll want to consider further testing. A high AFP can mean several things. Your baby produces AFP throughout your pregnancy, and a certain amount of it should cross the placenta into your bloodstream at each stage. If there's more than expected, it often means that you're carrying more than one baby or that your baby is older than your practitioner thought. But in some cases, it's a sign of an abnormal opening in the baby's spine (spina bifida), head or abdominal wall that's allowing more AFP to leak out. In rare cases, it can also signify a problem with the baby's kidneys. And in some cases, it doesn't mean any of those things. A low AFP, low estriol, and high hCG are associated with a higher risk for Down syndrome (trisomy 21). Low levels of all three mean your baby has an increased risk for trisomy 18, a more severe and less common chromosomal anomaly.
Certain results may also indicate that you yourself are at a somewhat greater risk for problems such as preeclampsia, premature birth, or miscarriage. Knowing this can allow you and your practitioner to be on the lookout for signs of trouble. If you receive an abnormal result, you'll most likely be offered a detailed (level II) ultrasound first. This test can be done right away and can give you immediate information. (If the ultrasound shows that your baby is younger or older than your practitioner thought, your results will be recalculated.) You may also want to meet with a genetic counselor at this point to discuss your risks and your options. If you have a high AFP, a level II ultrasound will confirm your baby's age and show whether you're carrying twins, and will allow your doctor to check your baby's spine and other parts for defects. If your baby is found to have spina bifida and you decide to continue the pregnancy, your medical team will be able to monitor your baby's condition during your pregnancy and prepare to do surgery once your baby's born. If you have a low AFP, the ultrasound can allow your doctor to check for several so-called "soft markers" that may suggest Down syndrome and other chromosomal disorders. These soft markers include cysts in a particular area of the brain (choroid plexus cysts), extra calcium in certain muscles of the heart (hyperechogenic intracardiac foci), a kidney problem (mild pyelectasis), a thickened nuchal fold (also called the nuchal translucency, a clear area between the back of the baby's neck and the overlying skin), an abnormally short thigh bone, and a bright-appearing (hyperechogenic) bowel.
When two or more of these markers are found, the chance that your baby has a chromosomal abnormality may be significantly higher, depending on your age and how far along you are. Also, a baby with a major structural abnormality, such as a defect in the heart or abdominal wall, has a greater chance of having a chromosomal defect. If everything looks normal on the ultrasound, it's not a guarantee that everything is okay, but it does mean that your baby has a lower risk of chromosomal defects than average for a woman your age. You may decide that this small risk is acceptable or you may decide that you'd also like to have amniocentesis to know for sure. If the ultrasound suggests your baby may have a chromosomal problem, your practitioner will usually recommend amniocentesis to determine for sure what's going on. And if the ultrasound detects certain structural defects, you may want amniocentesis to find out whether your baby has a chromosomal problem as well, which is often the case. Amniocentesis can diagnose 99 percent of chromosomal abnormalities, but it does carry a slight risk of miscarriage (one in 200 on average). This test is usually done between 15 and 20 weeks so that the parents will have the option of terminating the pregnancy before 24 weeks if they choose to. Again, you have to wait 10 to 14 days to get the results.
The main advantage of the multiple marker is that it can give you some information about your baby's risk of having certain birth defects without subjecting you to the slight risk of miscarriage associated with amniocentesis or the CVS test. If you're going to be 35 or older by your due date, your practitioner may suggest that you skip this test and go right to those more accurate tests. After you reach this age, your risk of having a baby with a chromosomal problem such as Down syndrome is higher than your risk of miscarrying because of amniocentesis. Still, if you're uncomfortable with this risk, you may choose to have the multiple marker with a detailed ultrasound instead. If the results of these are both normal, you may not want to go through with the amnio because the small chance that the baby will have a defect may now be less than the chance that an amnio would cause a miscarriage, just as it would be if you were younger than 35. Even if you know that you would never terminate a pregnancy for any reason, knowing in advance that your baby may have special needs allows you to prepare for the challenges you'll face. You might want to switch to a better-equipped hospital with specialists. Knowing what's going on with your baby will allow your medical team to monitor your pregnancy as needed and to bring a neonatologist or pediatric surgeon on board to prepare to help your baby after birth.
On the other hand, a false positive result can worry you needlessly (this is the most common complaint about the test) and make you decide to undergo amniocentesis for no reason. A false negative result could make you decide to avoid further tests that would have revealed a birth defect. Before making a decision, you'll want to discuss all of these issues with your partner, your health practitioner, and possibly a genetic counselor.
The multiple marker test measures your blood levels of three substances: alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3). For years, women were screened for AFP alone in a test called the maternal serum AFP or MSAFP, but now most labs check for all three substances because they can tell more that way. Some hospitals screen for the hormone inhibin A as well, in what's called a quadruple screen test. When this compound is added to the test, the detection rate for Down syndrome increases to between 67 and 76 percent in women younger than 35. It's usually done between 15 and 20 weeks of pregnancy, with 16 to 18 weeks (when the hormone levels are the most consistent) being the optimum time. You'll have a blood sample taken and sent to a lab for analysis. The lab analyzes the levels of AFP, hCG and uE3 (and sometimes inhibin A) in your blood and determines whether they fall within a "normal" range for this stage of your pregnancy, based on your age, weight, race, and other factors (such as having diabetes). Having too much or too little of these substances in your blood is considered a positive, or abnormal, result. Results are generally available in one or two weeks. Your level of AFP and the other substances are considered individually and in combination to determine whether you and your baby are at risk for certain problems. The results tell you what your baby's chances are of having each kind of birth defect. For example, on average, a 35-year-old woman has a 1 in 250 to 270 chance of having a baby with Down syndrome. If the results show that your chances of having a baby with any of the defects tested for are higher than average for your age, you'll want to consider further testing. A high AFP can mean several things. Your baby produces AFP throughout your pregnancy, and a certain amount of it should cross the placenta into your bloodstream at each stage. If there's more than expected, it often means that you're carrying more than one baby or that your baby is older than your practitioner thought. But in some cases, it's a sign of an abnormal opening in the baby's spine (spina bifida), head or abdominal wall that's allowing more AFP to leak out. In rare cases, it can also signify a problem with the baby's kidneys. And in some cases, it doesn't mean any of those things. A low AFP, low estriol, and high hCG are associated with a higher risk for Down syndrome (trisomy 21). Low levels of all three mean your baby has an increased risk for trisomy 18, a more severe and less common chromosomal anomaly.
Certain results may also indicate that you yourself are at a somewhat greater risk for problems such as preeclampsia, premature birth, or miscarriage. Knowing this can allow you and your practitioner to be on the lookout for signs of trouble. If you receive an abnormal result, you'll most likely be offered a detailed (level II) ultrasound first. This test can be done right away and can give you immediate information. (If the ultrasound shows that your baby is younger or older than your practitioner thought, your results will be recalculated.) You may also want to meet with a genetic counselor at this point to discuss your risks and your options. If you have a high AFP, a level II ultrasound will confirm your baby's age and show whether you're carrying twins, and will allow your doctor to check your baby's spine and other parts for defects. If your baby is found to have spina bifida and you decide to continue the pregnancy, your medical team will be able to monitor your baby's condition during your pregnancy and prepare to do surgery once your baby's born. If you have a low AFP, the ultrasound can allow your doctor to check for several so-called "soft markers" that may suggest Down syndrome and other chromosomal disorders. These soft markers include cysts in a particular area of the brain (choroid plexus cysts), extra calcium in certain muscles of the heart (hyperechogenic intracardiac foci), a kidney problem (mild pyelectasis), a thickened nuchal fold (also called the nuchal translucency, a clear area between the back of the baby's neck and the overlying skin), an abnormally short thigh bone, and a bright-appearing (hyperechogenic) bowel.
When two or more of these markers are found, the chance that your baby has a chromosomal abnormality may be significantly higher, depending on your age and how far along you are. Also, a baby with a major structural abnormality, such as a defect in the heart or abdominal wall, has a greater chance of having a chromosomal defect. If everything looks normal on the ultrasound, it's not a guarantee that everything is okay, but it does mean that your baby has a lower risk of chromosomal defects than average for a woman your age. You may decide that this small risk is acceptable or you may decide that you'd also like to have amniocentesis to know for sure. If the ultrasound suggests your baby may have a chromosomal problem, your practitioner will usually recommend amniocentesis to determine for sure what's going on. And if the ultrasound detects certain structural defects, you may want amniocentesis to find out whether your baby has a chromosomal problem as well, which is often the case. Amniocentesis can diagnose 99 percent of chromosomal abnormalities, but it does carry a slight risk of miscarriage (one in 200 on average). This test is usually done between 15 and 20 weeks so that the parents will have the option of terminating the pregnancy before 24 weeks if they choose to. Again, you have to wait 10 to 14 days to get the results.
The main advantage of the multiple marker is that it can give you some information about your baby's risk of having certain birth defects without subjecting you to the slight risk of miscarriage associated with amniocentesis or the CVS test. If you're going to be 35 or older by your due date, your practitioner may suggest that you skip this test and go right to those more accurate tests. After you reach this age, your risk of having a baby with a chromosomal problem such as Down syndrome is higher than your risk of miscarrying because of amniocentesis. Still, if you're uncomfortable with this risk, you may choose to have the multiple marker with a detailed ultrasound instead. If the results of these are both normal, you may not want to go through with the amnio because the small chance that the baby will have a defect may now be less than the chance that an amnio would cause a miscarriage, just as it would be if you were younger than 35. Even if you know that you would never terminate a pregnancy for any reason, knowing in advance that your baby may have special needs allows you to prepare for the challenges you'll face. You might want to switch to a better-equipped hospital with specialists. Knowing what's going on with your baby will allow your medical team to monitor your pregnancy as needed and to bring a neonatologist or pediatric surgeon on board to prepare to help your baby after birth.
On the other hand, a false positive result can worry you needlessly (this is the most common complaint about the test) and make you decide to undergo amniocentesis for no reason. A false negative result could make you decide to avoid further tests that would have revealed a birth defect. Before making a decision, you'll want to discuss all of these issues with your partner, your health practitioner, and possibly a genetic counselor.
Wednesday, October 31, 2007
The Female Evaluation
The infertility workup of the female partner has undergone several changes over the years but the basics have remained the same. The well-orchestrated female workup can be completed in a single menstrual cycle. At the end of this workup, along with the male data, the clinician should be able to plot a definitive course of treatment. The workup will be divided between female patients who are ovulatory by history and those that are not. Ovulation is presumed if the female has had regular menses every 26-32 days for the last six months. It is important to organize the workup to prevent unnecessary testing. The female workup should start with an initial intake that includes a thorough history, physical examination and a transvaginal pelvic ultrasound. Important historical details include those that might indicate previous exposure to STDs (such as a history of abnormal pap smears), recurrent pregnancy loss and the duration of infertility. Physical examination and pelvic ultrasound will identify patients that have gross pathology requiring surgical treatment prior to further fertility evaluation. For example, a dermoid cyst requiring surgery would allow the surgeon to evaluate tubal patency at the time of surgery rather than ordering an HSG.
Ovarian Reserve Testing
After the initial intake, the next step in the evaluation of the ovulatory female is the evaluation of ovarian reserve. The level of ovarian reserve and the age of the female partner are the most important prognostic factors in the fertility workup. Ovarian reserve is evaluated with a cycle day three FSH and estradiol level. On the third day of bleeding, a simple blood test yields a lot. Normal ovarian function is indicated when the FSH is <10 mIU/mL and the estradiol is <65 pg/mL. If the FSH is >15 mIU/mL, the patient will require egg donation. If the FSH is 10-15 mIU/mL or the E2 is >65 pg/mL, the more sensitive clomiphene citrate challenge test (CCCT) should be performed to further define ovarian reserve.
Tubal Patency
The next step in the ovulatory patient is to confirm tubal patency. This has been done traditionally with the hysterosalpingogram (HSG) and nothing has really improved on this. The HSG is performed at the outpatient radiology department. It involves injecting dye into the uterus and monitoring its "flow back" through the fallopian tubes. Blockages appear as concentrations of dye at the point of the obstruction. This test should be done in the follicular phase of the cycle after bleeding has stopped and before possible ovulation. The ordering physician should personally review the films to confirm findings of the study. Loculation of spill and tubal phimosis indicate that laparoscopy may be helpful. If large hydrosalpinges are identified, they should be clipped or removed laparoscopically prior to in vitro fertilization. Several large studies as well as a recent metanalysis, have confirmed the pregnancy rates with IVF are reduced by half in the presence of hydrosalpinges and that the rates are normalized with salpingectomy. The exact etiology of the phenomenon is not known.
Confirmation of Ovulation
Confirmation of ovulation is unlikely to be helpful in women when a careful history is consistent with ovulation. If there is doubt, a cycle day 21 progesterone with a level greater than 4 ng/mL is indicative of ovulation with most conceptions cycles having levels greater than 10 ng/mL. Alternately, sonographic confirmation of follicle rupture with serial ultrasound can be performed. Some programs use the basal body thermometer (BBT) to predict ovulation. The BBT measures the slight rise in temperature that occurs immediately prior to ovulation. Most physicians prefer to use the urinary ovulation predictor kits as they are more accurate and easy to administer.
Anovulatory Patients
The apparently oligomenorrheic patient should have the cause of their anovulation evaluated thoroughly prior to the initiation of treatment. The initial physical examination should note the presence or absence of goiter, acanthosis nigricans, striae, normal secondary sexual characteristics, Turner’s stigmata, galactorrhea, hirsuitism and abnormalities of the reproductive tract. Ultrasound should note the thickness of the endometrial lining as well as whether the ovaries are polycystic in nature. An endometrial biopsy should be considered if the uterine lining measures greater than 15mm.
Endocrine Evaluation
In anovulatory patients, the initial laboratory evaluation should include random levels of FSH, LH, prolactin, TSH, DHEAS and testosterone. Insulin resistance should be considered in patients that have any of the following: obesity, hirsuitism or acanthosis nigricans on physical exam; polycystic ovaries on ultrasound; inverted FSH/LH ratio or androgen excess on laboratory examination. Evaluation for insulin resistance can be accomplished simply with a 12 hour fasting serum insulin level. A 12 hour fasting serum insulin level of more than 10 mIU/ml signifies hyperinsulinemia in that PCOS subject.
Ovarian Reserve Testing
After the initial intake, the next step in the evaluation of the ovulatory female is the evaluation of ovarian reserve. The level of ovarian reserve and the age of the female partner are the most important prognostic factors in the fertility workup. Ovarian reserve is evaluated with a cycle day three FSH and estradiol level. On the third day of bleeding, a simple blood test yields a lot. Normal ovarian function is indicated when the FSH is <10 mIU/mL and the estradiol is <65 pg/mL. If the FSH is >15 mIU/mL, the patient will require egg donation. If the FSH is 10-15 mIU/mL or the E2 is >65 pg/mL, the more sensitive clomiphene citrate challenge test (CCCT) should be performed to further define ovarian reserve.
Tubal Patency
The next step in the ovulatory patient is to confirm tubal patency. This has been done traditionally with the hysterosalpingogram (HSG) and nothing has really improved on this. The HSG is performed at the outpatient radiology department. It involves injecting dye into the uterus and monitoring its "flow back" through the fallopian tubes. Blockages appear as concentrations of dye at the point of the obstruction. This test should be done in the follicular phase of the cycle after bleeding has stopped and before possible ovulation. The ordering physician should personally review the films to confirm findings of the study. Loculation of spill and tubal phimosis indicate that laparoscopy may be helpful. If large hydrosalpinges are identified, they should be clipped or removed laparoscopically prior to in vitro fertilization. Several large studies as well as a recent metanalysis, have confirmed the pregnancy rates with IVF are reduced by half in the presence of hydrosalpinges and that the rates are normalized with salpingectomy. The exact etiology of the phenomenon is not known.
Confirmation of Ovulation
Confirmation of ovulation is unlikely to be helpful in women when a careful history is consistent with ovulation. If there is doubt, a cycle day 21 progesterone with a level greater than 4 ng/mL is indicative of ovulation with most conceptions cycles having levels greater than 10 ng/mL. Alternately, sonographic confirmation of follicle rupture with serial ultrasound can be performed. Some programs use the basal body thermometer (BBT) to predict ovulation. The BBT measures the slight rise in temperature that occurs immediately prior to ovulation. Most physicians prefer to use the urinary ovulation predictor kits as they are more accurate and easy to administer.
Anovulatory Patients
The apparently oligomenorrheic patient should have the cause of their anovulation evaluated thoroughly prior to the initiation of treatment. The initial physical examination should note the presence or absence of goiter, acanthosis nigricans, striae, normal secondary sexual characteristics, Turner’s stigmata, galactorrhea, hirsuitism and abnormalities of the reproductive tract. Ultrasound should note the thickness of the endometrial lining as well as whether the ovaries are polycystic in nature. An endometrial biopsy should be considered if the uterine lining measures greater than 15mm.
Endocrine Evaluation
In anovulatory patients, the initial laboratory evaluation should include random levels of FSH, LH, prolactin, TSH, DHEAS and testosterone. Insulin resistance should be considered in patients that have any of the following: obesity, hirsuitism or acanthosis nigricans on physical exam; polycystic ovaries on ultrasound; inverted FSH/LH ratio or androgen excess on laboratory examination. Evaluation for insulin resistance can be accomplished simply with a 12 hour fasting serum insulin level. A 12 hour fasting serum insulin level of more than 10 mIU/ml signifies hyperinsulinemia in that PCOS subject.
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