Fertility Services
Additional Information on Services
Follicle Stimulating Hormone (FSH)
What Is FSH?
Follicle stimulating hormone (FSH) is a blood test used to evaluate men with semen abnormalities. This hormone is produced in the brain (specifically in the pituitary gland) and travels via the bloodstream to the testicles, where it stimulates the sperm production.
When Is FSH Obtained?
Follicle stimulating hormone (FSH) is measured whenever men are found to have one or more abnormalities on a semen analysis, such as issues with concentration, motility, or morphology. In some cases, FSH testing is conducted even in the absence of semen abnormalities.
How Is FSH Tested?
FSH is measured via a simple blood test.
How do you interpret results of FSH?
In men with sub-fertility or infertility, FSH results are generally interpreted as follows:
- Low (i.e. <1.0) = possible production issue of FSH within the brain. This usually requires additional testing, including a pituitary MRI and prolactin
- Normal (i.e. 1.0 to 4.5) = no abnormalities detected
- Mildly elevated (i.e. 4.6-7.5) = may suggest impaired sperm production
- Elevated (>7.5) = suggests impaired sperm production
These values are not applicable when men are undergoing hormone manipulation therapy, such as testosterone, clomiphene, anastrozole, HCG, or similar therapies.
Luteinizing Hormone (LH)
What Is LH?
Luteinizing hormone (LH) is measured in men who have infertility or testosterone abnormalities. This hormone is produced in the brain (specifically in the pituitary gland) and travels via the bloodstream to the testicles, where it stimulates the testosterone production and initiates sperm production. Intratesticular testosterone is necessary for the production of sperm.
When Is LH Obtained?
LH is measured whenever men are found to have one or more abnormalities on a semen analysis (such as concentration, motility, or morphology) or if they have abnormally low or high testosterone levels.
How Is LH Tested?
LH is measured via a simple blood test.
How do you interpret results of LH?
LH is typically interpreted along with testosterone levels to narrow down where the issues with testosterone production are occurring. LH results are generally interpreted as follows:
- Low (i.e. <1.0) = possible production issue of LH within the brain. This may require additional testing, including a pituitary MRI and prolactin. A low LH can also be due to other factors such as medications, testosterone supplementation, or other hormonal treatments.
- Normal (i.e. 1.0 to 4.5) = no abnormalities detected
- Mildly elevated (i.e. 4.6-7.5) = may suggest impaired testicular testosterone production
- Elevated (>7.5) = suggests impaired testosterone production
These values are not applicable when men are undergoing hormone manipulation therapy, such as testosterone, clomiphene, anastrozole, HCG, or other similar treatments. These therapies can result in lower levels (e.g. testosterone use), no change in levels, or higher levels (e.g., clomiphene [SERMs] or anastrozole).
Testosterone
What Is Testosterone?
Testosterone is measured via a blood test in men who have infertility or suspected testosterone level abnormalities. This hormone is produced in the testicles and is stimulated by luteinizing hormone (LH). Testosterone is critical for the initiation of sperm production and is also related to several symptomatic effects throughout the body, including overall energy, mood, muscle growth, fat mass regulation, bone mineral density, red blood cell production, erectile function, libido, and more.
When Is Testosterone Obtained?
From a fertility standpoint, testosterone is measured whenever men are found to have one or more abnormalities on a semen analysis (such as concentration, motility, or morphology). Men may also have their testosterone levels tested if they exhibit signs or symptoms of low testosterone, including erectile dysfunction, low libido, anemia, low bone mineral density, metabolic syndrome, depressed mood, diminished energy, difficulty concentrating, hot flashes, difficulty putting on muscle, or similar symptoms.
How Is Testosterone Tested?
Testosterone is measured via a simple blood test. The test should be conducted within a few hours of waking. Tests obtained in the afternoon (for men who wake in the morning) may be abnormally low by up to 30% or more. Ideally, if a man is found to have low testosterone, a second, confirmatory testosterone test should be obtained.
How do you interpret results of Testosterone?
Testosterone is typically interpreted along with LH to narrow down where the issues with testosterone production are occurring. Results are generally interpreted as follows:
- Very low (i.e. <150 ng/dl) = a repeat test is warranted. If the value remains this low, a pituitary MRI and prolactin should be obtained.
- Low (i.e. <300 ng/dl) = a repeat testosterone and LH should be obtained. If still <300 ng/dl, then the LH is reviewed. If it is low (i.e. <1.0), a prolactin and pituitary MRI should be obtained. If LH is high (i.e. >5-6), then this indicates that the testicle itself is likely the source of low testosterone.
- Normal (i.e. 300-1000) = no abnormalities detected
- Elevated (i.e. >1000) = the test is repeated along with LH. If it remains high, and if LH is high (i.e. >5-6), then a pituitary MRI and prolactin are recommended. If LH is low (i.e. <1.0), then external sources of testosterone are queried. If none are identified, then, a scrotal ultrasound is performed.
These values are not applicable when men are undergoing hormone manipulation therapy, such as testosterone, clomiphene, anastrozole, HCG, or similar treatment. It is very important to recognize that testosterone therapy using IM testosterone enanthate / cypionate / undecanoate, gels, oral, buccal, pellets, or other similar modalities can suppress LH and FSH and result in impaired sperm production. This is a very common cause of male infertility.
Estradiol
What Is Estradiol?
Estradiol is a blood test occasionally obtained in men who have infertility. This hormone is converted from testosterone in the fat cells of the body and is responsible for many symptomatic effects throughout the body, including mood, libido, erectile function, and others. Because estradiol is related to fat cells in the body, more obese men tend to have higher estradiol levels.
When Is Estradiol Obtained?
The role for estradiol in male infertility is somewhat controversial. Some practitioners routinely obtain this blood test in all men, while others do so selectively. Estradiol measurement is likely helpful in situations where men will be started on some form of hormonal therapy (such as clomiphene citrate or anastrozole). The test helps to identify the testosterone to estradiol ratio, which has been associated with abnormalities in sperm production within the testicle.
How Is Estradiol Tested?
Estradiol is measured via a simple blood test.
How do you interpret results of Estradiol?
The appropriate interpretation of estradiol is controversial. The most commonly agreed upon use of estradiol is in determining the testosterone to estradiol ratio. If the ratio is greater than 10:1 (e.g. testosterone 300, estradiol <30), then this is considered acceptable. In contrast, if the ratio is less than 10:1, this may indicate that hormonal manipulation should be done to correct this ratio.
In general, however, manipulation of estradiol levels as a primary treatment is not recommended, as this can lead to issues including reduced bone mineral density or other worsened symptoms.
Thyroid Stimulating Hormone
What Is Thyroid Stimulating Hormone?
Thyroid stimulating hormone (TSH) is a blood test that is occasionally performed in men experiencing infertility. This hormone is produced in the pituitary gland in the brain and helps regulate thyroid hormone levels in the body. Men with low thyroid hormone levels (hypothyroidism) may have impaired fertility, including lower sperm concentrations. Men who have low thyroid hormone and receive treatment to retore normal levels often experience improved sperm counts and motility.
When Is TSH Obtained?
Men with semen abnormalities, including low concentration or motility, are often recommended to have their TSH levels checked.
How Is TSH Tested?
Thyroid stimulating hormone (TSH) is obtained via a simple blood test.
How do you interpret results of TSH?
Men with a high TSH are recommended to undergo a confirmatory blood test for Thyroxine T4. If the T4 level is low, it suggests that the patient has hypothyroidism. In such cases, the patient may benefit from supplementation with medications such as levothyroxine (Synthroid). Supplementation of thyroid hormone has been shown to improve sperm concentration and motility in men with low thyroid hormone levels.
Semen Analysis
What Is a Semen Analysis?
A semen analysis is a laboratory test that checks for several abnormalities within the semen and helps to determine if a man is fertile. Although labs vary, the most important aspects of a semen analysis include assessment of the semen volume, pH, concentration (how many sperm), and motility (how many sperm are swimming). Sperm morphology (how sperm look / shape) is another aspect of semen analyses that is frequently tested, although it is likely not as important as the other factors mentioned above. Specialized sperm testing, such as DNA fragmentation index, is not a routine part of semen analyses.
How Is a Semen Analysis Obtained?
Semen analyses are obtained via ejaculation in the clinic, typically through manual stimulation (most common) or using a special collection condom. If possible, lubrication is avoided to prevent contamination of the specimen.
Although semen analyses can be obtained at home, it is generally not recommended. If a collection is done at home, a specialized container with specific fluid is provided to the patient. The sample should be returned to the clinic within one hour of collection and kept at body temperature during transportation.
How Long Does It Take to Get Results?
Depending on the time of day the sample is collected, results can be provided the same day or usually no later than the following day. A member of our staff will reach out by phone to discuss the results with you.
How Do You Interpret Semen Volume?
Semen volume should typically be in the 1.5 to 5.0 ml range. In cases where semen volume is consistently less than 1.0 ml, this can indicate several possible conditions:
- Retrograde ejaculation: Sperm goes backwards into the bladder (more common in diabetic males or those with deep abdominal surgery).
- Anejaculation: The seminal vesicles / prostate do not physically squeeze to ejaculate the semen. This is most commonly due to congenital causes (i.e., since birth), although on occasion, it can be related to medications such as Adderall.
- Absence of vas deferens: Some men are missing one or both vas deferens, often leading to a low volume, acidic (pH <7) ejaculate. It is also associated with other abnormalities of the kidneys and cystic fibrosis and should be investigated further.
- Ejaculatory duct obstruction: A relatively rare condition where a cyst, stone, or other obstruction prevents semen from being ejaculated from the ejaculatory duct in the prostate.
In cases where the semen volume is very large (particularly >10 ml), this can indicate:
- An open bladder neck: Typically, congenital (i.e. born with it), this occurs when the bladder neck is not closed at rest, leading to ejaculation of urine along with the sperm. This often results in sperm being present but not motile in the ejaculate. Sometimes, this can be treated with medications to close the bladder neck and allow ejaculation to proceed normally.
How Do You Interpret Semen Concentration?
Semen concentration should ideally be greater than 15 million/ml. Although concentration is not a perfect indicator of fertility, it is one of the better methods we have for determining why someone may be infertile. For example, there are men who have fewer than 5 million/ml who are fertile and men with 200 million/ml who are infertile. There are different ways of defining low sperm concentrations.
- Oligospermia: <15 million/ml
- Cryptozoospermia: Generally, <1 million/ml, though definitions may vary.
- Azoospermia: No sperm seen on at least two centrifuged specimens
Men with low sperm counts require further testing to determine the cause. This testing often includes examination of hormones in the blood, such as FSH, LH, and testosterone. Depending on the results, further blood tests may be conducted. In some cases, additional specialized testing, such as to check for cystic fibrosis, may also be obtained.
How Do You Interpret Semen Motility?
Semen motility should ideally be greater than 40%. This means that of all the sperm observed, more than 40% are moving. Among those sperm, a percentage will simply be twitching (less likely to fertilize), while others will be moving forward (progressive motility). Among all of the different sperm parameters, motility is likely the most important, as it predicts the ability to achieve a pregnancy.
Sperm with poor motility is referred to as asthenospermia.
Really low motility (0-5%) may indicate ciliary dyskinesia, obstruction (e.g., post-vasectomy reversal, ejaculatory duct obstruction), or decreased sperm production that halted several weeks prior to the semen analysis.
Men with low motility should generally undergo additional testing, such as FSH, LH, and testosterone.
Certain activities and treatments can increase motility in some cases, including more frequent ejaculation and treatments listed below.
How Do You Interpret Semen Morphology?
Semen morphology provides an estimate of how many sperm look completely normal (heads, midpiece, tails). The initial hope with this test was to predict fertilization potential by examining sperm appearance. However, multiple studies have confirmed that morphology is likely the least helpful of the various semen parameters (volume, pH, concentration, motility). Some studies suggest that morphology is no better at predicting fertility than flipping a coin (positive predictive value). The value of this test has largely been replaced by newer tests such as the DNA fragmentation index.
Sperm with low morphology is often referred to as teratospermia.
Men with low morphology (without any other abnormalities) generally do not require further evaluation. On occasion, men with low morphology and a history of recurrent miscarriages may benefit from further testing, such as the DNA fragmentation index. Similarly, no treatments have been consistently shown to improve morphology.
DNA Fragmentation
What Is DNA Fragmentation?
DNA fragmentation is a sperm test that assesses the DNA quality of the sperm overall and indicates the percentage of sperm with abnormal DNA. The test is most commonly used in couples pursuing IVF to determine the optimal source of sperm, whether from the ejaculate or directly from the testicle.
How Do You Interpret DNA Fragmentation?
This is actually somewhat of a complicated answer. There are several different methods for obtaining DNA fragmentation, and each is interpreted slightly differently. Also, there are relatively limited studies that have compared testing methods and clearly identified what is normal and abnormal. In general, the higher the DNA fragmentation, the more likely the patient is to experience subfertility, miscarriages, and failed IVF cycles. In our practice, we tend to prefer the SCSA method and set the point of abnormal at 15%. This means that if your DNA fragmentation is >15%, and you're undergoing IVF, we will recommend that sperm be obtained from the testicles directly rather than from the ejaculate.
How Does DNA Fragmentation Help During IVF?
Men who have high DNA fragmentation (typically >15-30% abnormal) in the ejaculate often have much lower DNA fragmentation from sperm obtained from the testicles (typically around 5%). When sperm with high DNA fragmentation are used in IVF, the live birth rates are lower than when sperm with lower DNA fragmentation is used. Because of this, men with high DNA fragmentation in ejaculated sperm are often recommended to have sperm retrieved from the testicles (TESE) to use with IVF. Several studies have shown that this can nearly double the live birth rates.
How Expensive Is DNA Fragmentation
The price is variable depending on the specific type of testing that is obtained. Prices often range from $450 to $700+. Insurance does not cover this particular test.
Transrectal Ultrasonography
What Is Transrectal Ultrasonography?
Transrectal ultrasonography (TRUS) is an ultrasound test performed to evaluate for abnormalities of the ejaculatory duct. It involves placing an ultrasound probe in the rectum to view the prostate gland.
When Is Transrectal Ultrasonography Performed?
The test is most often performed in men with low ejaculate volumes (<1 ml), with or without abnormal semen pH (<7.0). It is the preferred test for detecting ejaculatory duct abnormalities and can detect prostatic cysts or dilated seminal vesicles (i.e. due to an ejaculatory duct stone).
How Often Are Abnormalities Truly Identified on TRUS?
Although published rates of ejaculatory duct obstruction range dramatically (<1% to >30%), in our experience, true ejaculatory duct obstruction is very rare and is often inappropriately diagnosed. In men with obstructive azoospermia, testicular biopsy and fine needle vasography are much better at identifying the true cause of obstruction and are able to rule out ejaculatory duct causes in the vast majority of men.
Fine Needle Vasography
What Is Fine Needle Vasography?
Fine needle vasography is a test that evaluates whether the vas is blocked from a location a few centimeters above the testicle through the ejaculatory duct. The test requires a minor surgical procedure where the vasa are identified on each side and a small catheter is placed within the lumen. Fluid is instilled, and pressures are assessed to determine if a blockage is present.
When Do You Use Fine Needle Vasography?
Fine needle vasography is often combined with a testicular biopsy in cases where men have azoospermia due to a suspected obstructive cause. Examples include men with normal testicular size and normal FSH levels. In these men, causes for obstruction may be acquired (e.g., following inguinal hernia repairs, genital infection, trauma) or may have been present since birth (epididymis and/or vas didn't develop normally). Some of these causes may be repaired surgically, while others may not.
How Is Vasography Interpreted?
In men with azoospermia where sperm are present in the testicle and vasography is negative (no evidence for blockage), these men are candidates for bilateral epididymovasal reconstructions. These are successful in approximately 50% of cases at restoring sperm to the ejaculate sufficient to achieve a pregnancy. In certain cases where obstructions are identified in the vas (e.g., after inguinal hernia repairs), these may also be repaired using robotic-assisted vasovasostomies. However, if sperm are not present in the testicle, or in most cases where obstructions are identified in the vasa, this suggests that reconstruction is not an option, and in-vitro fertilization is likely required (if possible).
Is There Anything Else Important About Fine Needle Vasography?
It is important to distinguish this from traditional vasography. With traditional vasography, the vas deferens is cut apart, and fluid is instilled. This traditional technique is much more invasive and permanently damages the vas. It should only be performed if the patient is planning on performing a reconstruction during the same surgery.
In contrast, fine needle vasography is a test that helps determine if the patient is even a candidate for reconstruction before committing to that surgical procedure. This is particularly helpful since fine needle vasography determines in advance whether the patient has a chance for success with reconstruction, rather than only finding out in the middle of the procedure. It can therefore save many men from undergoing an unnecessary procedure.
Testicular Biopsy
What Is a Testicular Biopsy?
A testicular biopsy is when testicular tissue is sampled using a needle or surgical extraction to perform testing. Biopsies are most often performed to determine if sperm are present in the testicle itself. When examined by a pathologist, a testicular biopsy can also help to narrow down where sperm issues are occurring (i.e. maturational arrest, Sertoli only syndrome, etc.).
When Is a Biopsy Obtained?
Testicular biopsies are most often obtained in men with azoospermia (no sperm in the ejaculate), normal sized testicles, and a normal FSH (<4.6, in particular). This helps to determine if sperm are being produced or not, and it can be performed along with fine-needle vasography to help determine if the man is a candidate for epididymovasal reconstruction.
Are Biopsies Covered By Insurance?
In most cases, testicular biopsies are covered by insurance.
How Do I Interpret the Findings from a Biopsy?
In most cases (and in our practice), a testicular biopsy is performed to determine if sperm can readily be identified or not. It is also possible to obtain additional testing from a biopsied specimen, such as whether the patient has Sertoli Only Syndrome, maturational arrest, or other similar issues. However, in our practice, we have found that these other syndromes do not provide much additional benefit and end up costing the patient more. They also do not guide clinical decision making, as outcomes of surgical procedures, such as microTESE are either not impacted or are minimally impacted by this information.
Semen Cryopreservation
What Is Semen Cryopreservation?
Semen cryopreservation is the freezing of sperm to keep it stored. Although no one knows how long sperm may be safely stored, there are examples of successful use of sperm that has been frozen for several decades. In reality, sperm may likely remain successfully frozen for >100 years or more if desired. Once frozen, sperm are stored in liquid nitrogen to keep it preserved.
When Is Semen Cryopreservation Performed?
Semen cryopreservation is most often performed in cases where men will be undergoing some form of treatment that may impact their fertility. Examples include chemotherapy and radiation. Semen cryopreservation is not required in cases of a vasectomy or at the time of vasectomy reversal. This is because sperm can still be retrieved at a future time if needed directly from the testicles.
How Many Samples Should Be Obtained?
When performed prior to chemotherapy, we typically recommend obtaining 3 separate ejaculated specimen for cryopreservation, separated by at least 1-2 days when possible. These additional specimen are often needed because men who have a malignancy (cancer) often have lower sperm counts and will only have small numbers in each ejaculate.
How Are Frozen Sperm Used?
In cases where sperm are cryopreserved due to treatments such as chemotherapy, frozen sperm should ONLY be used with in-vitro fertilization and should NOT be used for intrauterine insemination. This is because men who have cryopreserved prior to chemotherapy likely only have a certain number of vials frozen. And given the lower success rates with intrauterine insemination and the finding that approximately 90% of sperm will lose their motility with freezing (leading to lower numbers available with intrauterine insemination), if cryopreserved samples are used with intrauterine insemination, it may lead to a loss of all viable samples. In contrast, couples using a sperm donor will most often use cryopreserved ejaculated specimen.
TESA / TESE
What Is a TESA or TESE?
A TESA is a testicular sperm aspiration, while a TESE is a testicular sperm extraction. Both procedures involve obtaining sperm directly from the testicle for use with assisted reproductive techniques. In the case of TESA, typically, a large needle is inserted into the testicle, and testicular tissue (seminiferous tubules) is withdrawn. With TESE, a small incision is made into the testicle, and testicular tissue is obtained.
When Is TESA/TESE Performed?
These procedures are most often used to obtain sperm from the testicles in two scenarios. The first case is when there is an obstruction that results in no sperm being in the ejaculate. This is most often seen in men who have had a vasectomy, but it can also occur in other cases that lead to blockages. The second case occurs in couples who are undergoing in-vitro fertilization where the man either has an elevated DNA fragmentation index (i.e. sperm have a high rate of DNA problems) or when his sperm count is otherwise abnormal (and an abnormal DNA fragmentation is being assumed). In those cases, sperm from the testicle are used preferentially over ejaculated sperm to optimize the chances for a live birth with IVF.
Is TESA or TESE Better?
There are advantages and disadvantages to either approach. TESE is generally considered the gold-standard method of sperm retrieval, as it is able to gather a larger amount of sperm (and thus, repeat procedures to retrieve sperm are usually not required). TESE procedures also arguably have lower rates of hematoceles and hydroceles (complications), as any bleeding or extra tunica can be taken care of at the time of the procedure. TESA is a less complex procedure and is most often less expensive than a TESE.
What Is the Difference Between TESE and microTESE?
A TESE procedure is a much less complex procedure, is less invasive, and is less expensive. TESEs are typically performed when patients have either sperm in their ejaculate or have a clear cause of obstruction (i.e. prior vasectomy). In contrast, microTESE procedures are much more complicated and have higher complication rates. microTESE procedures are typically reserved for cases where the patient has no sperm in the ejaculate (azoospermia) and where the cause of the azoospermia is due to the absence of production of sperm (i.e. not due to a vasectomy or other cause of obstruction).
PESA / MESA
What Is a PESA or MESA?
A PESA is a percutaneous epididymal sperm aspiration, while a MESA is a microscopic epididymal sperm aspiration. A PESA is performed by passing a needle through the scrotal skin into the epididymis. Epididymal fluid is then suctioned to retrieve sperm. With a MESA, an incision is made in the scrotum and the epididymis exposed. A few tubules are then incised and sperm retrieved. Although there is debate as to the merits of PESA or MESA, in general MESA is considered the gold-standard between the two because of larger retrieval rates, lower contamination with blood (blood kills sperm), and less overall trauma to the epididymis. PESA is generally less expensive than MESA and does not require specialized training to perform.
When Is PESA/MESA Performed?
These procedures are most often used to obtain sperm for in-vitro fertilization when sperm is blocked from something such as after a vasectomy. Although technically enough sperm could be retrieved from a MESA for use with one fresh intrauterine insemination attempt, this is generally not performed or recommended due to a lack of data showing any efficacy, lower intrauterine insemination success rates overall, and the need to perform a MESA with each attempt. The bigger debate is whether PESA/MESA or TESA/TESE sperm should be used with in-vitro fertilization cases when the patient has had a vasectomy and is not pursuing in a vasectomy reversal. The preferred technique has not been fully proven, although there is some evidence suggesting that MESA may be slightly superior in this setting.
Can sperm from a PESA/MESA be frozen?
Yes. In most cases, sperm may be frozen after the procedures to use with future in-vitro fertilization cycles.
microTESE
What Is a microTESE?
A microTESE is a very specialized method of sperm extraction that is typically reserved for men who have no sperm (azoospermia) due to a production issue. It is much more invasive than a typical TESE procedure, but it may increase the chances slightly compared to a TESE for identifying and retrieving sperm.
When Is microTESE Performed?
This procedure is typically reserved for cases where men have no sperm (azoospermia) and where it is believed that this is due to a problem with sperm production (rather than obstruction / blockage). It is also performed in cases where men have had a previous, unsuccessful TESE procedure.
How is a microTESE performed?
MicroTESE procedures involve opening up the testicle to expose the seminiferous tubules. The tubules are then examined using an operating microscope to attempt to identify regions of greater sperm production. The key principle behind microTESE procedures is increasing the likelihood of finding sperm at the time of IVF/ICSI (in-vitro fertilization / intracytoplasmic sperm injection). Because of the small numbers of sperm retrieved with microTESE, it cannot be used for intrauterine insemination.
What are complications of a microTESE procedure?
MicroTESE procedures are much more invasive and complicated compared to TESE procedures and usually require a longer period of recovery. The main risks are similar to other scrotal procedures, including infection, hematoma, and chronic pain. In contrast to TESE procedures, they can also reduce testosterone production slightly compared to pre-operatively.
What are success rates of a microTESE?
Success rates with microTESE strongly depend on the definition of success utilized. In men who are truly azoospermia (no sperm) due to a production issue (not blockage), the chance of finding sperm is variously reported at 30-70%. When a more strict definition is utilized, such as, sufficient sperm are able to be identified at the time of IVF/ICSI (in-vitro fertilization / intracytoplasmic sperm injection), the success rate drops to 15-30%. If the definition of a live birth is used, the success rates are typically 5-10%.
Reference: Boeri L, et al: Andrology 2020 Jan (epub); PMID 31999885
Clomiphene Citrate
What is Clomiphene citrate (Clomid)?
Clomiphene citrate is a medication that partially blocks some estrogen in the body. It is commonly used in both men and women to increase the chances of pregnancy. Although women typically are only able to take it for a short period of time, men may take it for many months or years. Because of the large number of studies reporting its use, the relatively low side effect profile, and costs, clomiphene is one of the most commonly used medications for men with infertility.
What is the optimal dosing for clomiphene?
No one knows for sure. One specific study that looked at 5 separate studies found that the full 50 mg dose daily is required to see a benefit, whereas the 25 mg (half pill) dose is inadequate. Long-term use of clomiphene may lead to tacchyphylaxis, which means that the body gets used to the medication, and it is no longer effective. Because of this, it is our preference to use 50 mg daily x 3 weeks, followed by a 1-week break, and then repeated monthly.
How long does it take for clomiphene to be effective?
Although the exact time when clomiphene achieves its maximal benefits is not well studied, it likely takes 6-9 months to reach its peak efficacy.
How effective is clomiphene in men?
In men who are appropriately chosen for clomiphene, the medication may increase the chances for spontaneous pregnancy over the next 12 months by up to 5x (based on one meta-analysis of 5 separate studies).
Who are good candidates for clomiphene?
Although the optimal candidate for clomiphene isn't fully studied, it likely does best in men who have low sperm concentrations and/or motility and who have a normal FSH (blood test).
Anastrozole (Arimidex)
What is anastrozole (Arimidex)?
Anastrozole is an "aromatase inhibitor" that works by blocking the conversion of testosterone to estradiol in the body. By doing so, the estradiol is not able to 'feed back' to the hypothalamus and pituitary. This then increases the release of FSH and LH from the pituitary gland, which then stimulates the testicles to make more sperm and testosterone. It also impacts the ratio of testosterone to estradiol within the testicles, which may improve sperm production.
What is the optimal dosing for anastrozole?
There is wide variability among infertility specialists on anastrozole dosing. Recommended doses range from 1 mg daily to 1 mg weekly. The optimal dose is currently unknown.
Are there any side effects of anastrozole?
Yes. Anastrozole tends to have the most side effects of any of the male hormone therapy options, and therefore it is less often recommended. Specifically, since anastrozole decreases estradiol in the body, it can lead to decreases in libido, erectile function, energy, and, over time, decreases in bone mineral density (thin bones or osteopenia / osteoporosis). Because of the longer-term risks, the use of anastrozole beyond one year is less commonly recommended.
Human Chorionic Gonadotropin (HCG)
What is HCG?
HCG stands for human chorionic gonadotropin, as it is a hormone that is normally produced by certain cells in the placenta known as syncytiotrophoblasts. In men, the hormone functions similar to luteinizing hormone (LH) by stimulating Leydig cells in the testicles to produce testosterone.
When is HCG used?
HCG is mostly used in situations where testosterone production is desired from the testicles directly rather than from external testosterone preparations. In contrast to external preparations of testosterone, HCG typically does not lead to testicular shrinkage (atrophy) or reduced sperm counts (although with really high testosterone levels, sperm production can still be impaired, even when HCG is used).
HCG is ideally used for cases where LH production is inadequate, such as pituitary insufficiency (e.g. Kallmann Syndrome) or other "hypogonadotrophic hypogonadism" conditions.
HCG is not effective in certain situations. As HCG requires normally functioning testicles, it is often not effective at increasing testosterone levels in men with Klinefelter Syndrome or other causes of gonadal failure. In select cases, HCG may be combined with external testosterone to preserve fertility.
What are the down sides to using HCG?
HCG is often a much more expensive way of administering testosterone, and as such, alternative fertility preserving options such as Clomid are more commonly used. Doses of HCG used during the treatment of male-factor infertility can range from 500 units twice weekly to 5000 units 3x per week, with dosages adjusted based on testosterone levels.
Human Menopausal Gonadotropin (HMG)
What is HMG?
HMG stands for human menopausal gonadotropin and represents substances that are retrieved from the urine of pregnant women. Most HMG preparations contain a high percentage of follicle stimulating hormone (FSH) and a smaller amount of luteinizing hormone (LH). Both FSH and LH are important substances that help to regulate sperm and testosterone production.
When is HMG used?
HMG is not commonly used to treat male fertility in the US. Although it is an effective FSH replacement, it is very expensive and has not been shown to be superior to less expensive options, such as Clomid in nearly all cases. In certain conditions, HMG (or other FSH replacement therapies) must be used, such as with hypogonadotropic hypogonadism (e.g. Kallmann syndrome). However, these conditions are relatively rare and account for <1% of all infertility cases seen.
What are the down sides to using HMG?
The main down side to using HMG is cost. If HMG were not so expensive, it likely would be used more commonly to treat several conditions associated with male infertility, including men with low sperm counts. However, because the costs are so high, alternative therapies such as Clomid, HCG, and anastrozole are much more commonly prescribed. Each of these medications has distinct uses, benefits, and side effects for certain conditions.
Varicocelectomy
What is a varicocele and varicocelectomy?
A varicocele is the term used to describe dilated veins in the blood supply going to the testicle (spermatic cord). The exact cause of varicoceles is not known, although it may relate to the failure of small valves within the veins that drain blood from the testicles. These valve failures then lead to greater pooling of blood and expansion (dilation) of the veins. A varicocele most often occurs with the left testicle, and this is thought to occur because of the difference in how blood drains from the right (to the vena cava) and left (to the left renal vein) testicles. Varicoceles can occur at any age, and they may be worsened or brought on by activities such as weight lifting or other similar strenuous movements.
Varicocelectomy technically refers to a surgical procedure in which the veins are cut, however, it is often more broadly used to describe any technique that blocks the blood flow in these veins (including embolization).
How common are varicoceles?
Varicoceles are estimated to occur in approximately 15% of men. Some studies suggest that this rate may be higher among men who have infertility or may occur more commonly in some families (genetic link).
How are varicoceles graded?
Varicoceles are graded on a scale of 0-3:
- Grade 0 = found only on ultrasound
- Grade 1 = able to feel when the patient performs a valsalva-type of maneuver (e.g. bearing down, like as with a bowel movement)
- Grade 2 = able to feel easily with standing
- Grade 3 = able to see the lumps/bumps of a varicocele through the scrotal skin
In our clinical experience, men with grade 2-3 varicoceles are much more likely to already know that they have a varicocele and will describe a feeling of a "bag of worms" in the scrotum. This is often more easily recognized after standing for extended periods of time, particularly in warmer temperatures. In contrast, men with grade 0 and 1 varicoceles often do not recall any symptoms of a varicocele and are typically told that they have one at the time of a scrotal ultrasound or examination.
Are varicoceles linked to any dangerous health conditions?
In most cases, varicoceles are not linked to any dangerous health conditions. This is particularly true when the varicocele has been present lifelong. However, if a varicocele is new in onset or rapidly changing, it is important to obtain some form of imaging (ultrasound, CT, MRI) to make sure that nothing more serious is occurring. As an example, in our practice, we have treated patients who had previously unknown blood clots in their renal vein, cancers such as lymphoma, or other serious conditions that first appeared as a new varicocele.
In cases where a varicocele is present lifelong, the varicocele may sometimes impact the growth of a testicle. In cases where the testicles are not growing at a similar rate on each side, a varicocelectomy is usually recommended sooner rather than later to prevent further impairment in testicular growth and production.
Currently, it is not clear whether an untreated varicocele can cause progressive loss of fertility over time. Similarly, it is not clear if treating a varicocele prevents further loss of fertility over time. Although these are not fully known, many male infertility specialists (including our practice) feel that it is important to treat a varicocele in men who have different testicular sizes and/or younger men (i.e. 20's) who have difficulty conceiving or who have impairments in semen parameters (i.e. abnormal sperm test).
When should a varicocele be treated?
The treatment of varicoceles has remained a controversial topic for several decades, as the research behind the benefits of varicocele surgery is often contradictory. In general, most male fertility specialists would recommend treating the following:
- A grade 2 or 3 varicocele in a couple that is having difficulty conceiving and where the man's semen analysis demonstrates abnormalities of concentration, motility, and/or morphology
- A teenage child where the testicle sizes are different (discrepant)
- A man with bothersome, varicocele-like testicular pain
There are certain scenarios where some male fertility experts would also offer a varicocelectomy, although these are more controversial:
- A couple with unexplained infertility and no semen analysis abnormalities
- Grade 1 varicoceles
- A man with semen analysis abnormalities and unknown ability to achieve a pregnancy
And there are certain scenarios where a varicocelectomy should not be offered:
- Men with grade 0 varicoceles (found only on ultrasound)
What is the best way to treat a varicocele?
There are many different methods that have been described to treat varicoceles, including laparoscopically, radiographic embolization, and inguinal / subinguinal ligation with or without the assistance of an operating microscope.
Although there is some ongoing controversy on the optimal method of treatment, most clinical studies (meta-analyses) suggest that the microscopic subinguinal varicocelectomy is the best approach. This is because it is thought to have the lowest recurrence rate and highest overall success rate. In our clinical experience, we also agree with this statement, and because of this, we only recommend the microscopic subinguinal approach for treating varicoceles.
Epididymovasostomy (EV)
What is an epididymovasostomy?
An epididymovasostomy, or EV for short, is a surgical procedure where the vas deferens is attached to the epididymis using an operating microscope. This procedure is most commonly performed during a vasectomy reversal, when the area of blockage is at the level of the epididymis. However, it is also performed in some men with obstructive azoospermia (i.e. no sperm in the ejaculate due to an obstruction somewhere).
Which men are appropriate for an EV procedure?
Only a small percentage of men will be appropriate for this surgical procedure (excluding men with prior vasectomies - for more information on vasectomy reversals, visit the vasectomy reversal portion of our website).
Men who have azoospermia (no sperm) or severe cryptozoospermia (typically <100,000 sperm per milliliter) may undergo additional testing to determine if they have low numbers because of a blockage or because of a production issue. Azoospermic men with normal FSH levels (blood hormone) and normal testicular sizes are more likely to have a blockage issue leading to their low sperm counts. In these men, we typically recommend performing a combined testicular biopsy and fine-needle vasography procedure. This is able to determine #1 if sperm are being adequately produced in the testicles, and #2 if the tubes that normally deliver the sperm to the ejaculate are fully intact. If that testing comes back appropriate (meaning sperm are being produced in the testicles, and fluid is able to travel through the vas), then the patient is a candidate for an EV procedure.
What are the risks and benefits of an EV procedure?
In men who are appropriate candidates for an EV procedure, there are notable benefits:
- Possibility of a return of sufficient sperm to the ejaculate to be able to achieve a pregnancy (roughly 60% overall success rate)
- Ability to have more than one child if successful (long-term benefit)
There are also potential risks and side effects of surgery:
- Testicles are typically higher-riding in the scrotum (at least for several months)
- Recovery is uncomfortable for several weeks
- Small chance of chronic testicular pain which may last months or years in some cases
- Risk that surgery doesn't work
- Financial costs (typically not covered by insurance - our current prices are listed here)
What is a vasectomy reversal?
A vasectomy reversal is a surgical procedure where sperm is restored to the ejaculate in a man who previously underwent a vasectomy. The procedure most often involves an operating microscope and may include a vasovasostomy (VV) or epididymovasostomy (EV). For more information on vasectomy reversals, please visit the main portion of our website dedicated to vasectomy reversals.
How successful are vasectomy reversals?
Success rates with vasectomy reversals are highly dependent upon the experience of the reversal surgeon and whether or not the reversal surgeon is able to perform both a vasovasostomy (VV) or epididymovasostomy (EV) if needed. Because of this, success rates may be as low as 30% among low volume surgeons, 70-80% among high volume surgeons who do not perform EVs, or 95% among high volume surgeons who perform both VVs and EVs. For more specific information on vasectomy reversals, or to receive a customized success rate, please visit the main portion of our website dedicated to vasectomy reversals.
What are the risks and benefits of a vasectomy reversal procedure?
Of men who have previously had a vasectomy, the potential benefits of a vasectomy reversal include:
- Possibility of a return of sufficient sperm to the ejaculate to be able to achieve a pregnancy
- Ability to have more than one child if successful (long-term benefit)
- More cost-effective and lower risk to female partner than in-vitro fertilization
There are also potential risks and side effects of surgery:
- A full 8-week recovery is recommended to optimize outcomes
- A repeat vasectomy may be desired at a later date
- Small chances of infection, hematoma, or chronic testicular pain
- Risk that surgery doesn't work
- Financial costs (typically not covered by insurance - our current prices are listed here)
For more information on a vasectomy reversal, please visit our main webpage dedicated to vasectomy reversals.
Transurethral Resection of Ejaculatory Duct
What is a transurethral resection of the ejaculatory duct (TURED)?
Transurethral resection of the ejaculatory duct (TURED) is a surgical procedure that is used to unblock the ejaculatory duct in the prostate. Ejaculatory duct obstruction is a relatively rare condition, and it is typically associated with specific abnormalities of the semen analysis, including low pH (<7), low sperm counts, low motility, and consistently low volume (<1 ml). In some cases, blockage of the ejaculatory duct is temporary (i.e. blood clot), while in others, it may be more permanent (stone or cyst).
A TURED procedure is performed under anesthesia and involves placement of a rigid scope through the opening of the penis. The area of obstruction is observed, and a cautery loop is then advanced from the scope to cut out the blocked area. The procedure is fairly rapid and is done as an outpatient (no hospital admission required).
How is an ejaculatory duct obstruction diagnosed?
This condition is most often diagnosed through the use of an ultrasound probe that is placed in the rectum. The prostate and seminal vesicles are then visualized to look for specific findings, including dilated seminal vesicles or prostatic cysts. Men who are most at risk of an ejaculatory duct obstruction are those with consistently low volume ejaculates (<1 ml) and abnormalities of the semen (pH <7.0, low concentration - particularly <100,000/ml, and low motility). The condition may be present lifelong or be new in onset.
What are the risks and benefits of TURED?
The potential benefits of a TURED procedure include:
- Restoration of normal volumes, sperm counts, and motility to the ejaculate
- Improved ability to achieve a pregnancy spontaneously
The potential down sides to TURED include:
- Chronic testicular pain (thought to be due to retrograde flow of urine through the ejaculatory duct) - this is the main risk and is fairly common. Symptoms may last days or even years in some cases.
- Lack of improvement in ejaculate volume, sperm counts, or motility. Unfortunately, diagnostic methods of identifying an ejaculatory duct obstruction are not perfect, and in many cases, resecting the ejaculatory duct may not improve the underlying problem.
- Re-closure or repeat obstruction of the ejaculatory duct after an initial improvement. The rate of this is not known, given the relative rarity of the procedure overall.