Showing posts with label azoospermia. Show all posts
Showing posts with label azoospermia. Show all posts

Thursday, October 11, 2018

News from ASRM 2018: Some interesting research papers on male factor infertility


The American Society of Reproductive Medicine just wrapped up its 2018 scientific congress and expo at Denver, Colorado.  Here are some of the research highlights presented at the society about male factor infertility. 

A diagnosis of azoospermia puts men at increased risk of death


Results of a large prospective cohort study report a link between azoospermia and increase the risk of mortality. The study findings were jointly presented by Scandinavian and American researchers at the meeting. Interestingly, the increased risk of dying was not observed for men with oligospermia. 

The authors analyzed data of 51,289 men from the Danish National IVF register from 2006 through 2016 and followed those with azoospermia till the end of study period, death or till they emigrated from Denmark. Vasectomized men and men with normal semen parameters were used as a reference.
The average follow-up period was eight years. Men with azoospermia faced twice the increased risk of dying as compared to men with oligospermia and normal semen parameters.  The mean age at death was 48.8, and the most common cause of death was CVD and cancer.  

Another previous cohort study from Denmark also documented that as the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05).

Peter Schlegel, MD, ASRM President-Elect, noted, “A man’s infertility status is a component of his whole health status. Semen analysis results exist on a continuum, but a diagnosis of azoospermia may be a call to take a closer look at a man’s overall health in addition to his reproductive function.”
Thus, Semen parameters could be a key biomarker of overall male health.


Inadequate sleep is linked to Low Testosterone Levels in Men

Lack of sleep is associated with decreasing testosterone levels in US male reports the results of a study presented at the ASRM scientific congress at Denver, Colorado. The other culprits for low testosterone were aging, increasing BMI and alcohol consumption.

The researchers examined the data on nearly 2300 males, aged 16-80 years from The National Health and Nutrition Examination Survey (NHANES). The subjects reported an average sleep duration of 6.86 hours (2-12 hours) and had average serum testosterone levels of 303.33 ng/dL (43.39 ng/dL to 779.2 ng/dL).

After accounting for confounders, the researchers noted that serum testosterone levels decreased by 0.49 ng/dL per year of age, 5.85 ng/dL per lost hour of sleep, 6.18 ng/dL per BMI unit increase, and 2.99 ng/dL per each unit increase in alcohol consumption.

Robert Brannigan, MD, a member of ASRM’s Board of Directors, remarked “Reduction in testosterone level can have deleterious effects on a man’s health beyond his fertility and sexual function.  Testosterone is essential for good metabolic function and decreased levels of the hormone are associated with metabolic syndrome and cardiovascular disease.  Low testosterone can contribute to fatigue and depression, as well. A balanced diet and a healthy sleep routine are interventions a man can take on his own to help keep his T levels stable.”


A decline in sperm count and motility observed in North America and Europe

Two studies presented at the ASRM scientific congress showed that semen quality has seen a decline in patients undergoing fertility treatment and donors in this century. In the first study, researchers from one European and the other North American center evaluated the results of semen analysis from 119,972 men seeking infertility treatment between 2002 through 2017.

The researchers looked at the most reliable indicator of male fertility, the total motile sperm count (TMSC) and grouped the study population into 3 groups: TMSC greater than 15 million; TMSC 5 to 15 million: and TMSC zero to 15 million.

The percentage of patients in Group 1 (highest TMSC) declined from 84.7% in the time period 2002-2005 to 79.1% in 2014-2017, while the percentage in Group 3 (lowest TMSC) rose from 8.9% to 11.6% over those time periods.

TMSC decreased by 1.1% per year as the men aged and thus patients who belonged to Group 1 were slowly slipped into Group 2 as they age.   

For the second study researchers from the Ichan School of Medicine at Mount Sinai, California Cryobank, and Reproductive Medical Associates of New York observed a progressive decline in semen quality in donors over 11 years in six cities:  Los Angeles, Palo Alto, Houston, Boston, Indianapolis, and New York City.

Over a period of 10 years, the researchers analyzed 124,107 semen specimens provided by 2586 donors aged 19 to 38. They looked at three semen parameters- total count, average concentration, and TMSC-  as a whole and region by region.

A decrease in all three parameters was observed in all regions, except New York. ASRM President-elect Peter Schlegel, MD, said, “The trend toward lower sperm counts in this study is concerning.  Whether the causes underlying it are environmental or lifestyle-related, they will be difficult to parse out.  Pollution, endocrine disrupting chemicals, poor exercise habits and convenient, yet nutritionally poor, dietary choices could all play a part.  Similarly, men may now be referred for advanced medical care despite having lower sperm numbers, reflecting our improved reproductive treatments.  Men planning to conceive should do what they can to achieve their best overall health to optimize their sperm quality.”



Sunday, September 30, 2018

How to evaluate the azoospermic male? ASRM committee recommendations


The Practice Committee of the American Society for Reproductive Medicine (ASRM) in collaboration with the Society for Male Reproduction and Urology recently issued guidelines about the diagnosis and evaluation of the azoospermic male partner. The committee opinion was published recently in journal Fertility and Sterility.

Of all the infertility cases about 30% is because of ‘male-factor’ of whom about 10-15% of men will receive the diagnosis of azoospermia. Recent studies have documented a decline in sperm count globally with a concurrent increase in male factor infertility.

Azoospermia is classified into 3 categories-pre-testicular, testicular, and post-testicular according to the etiology but in clinical practice, azoospermia is commonly classified as obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) which can be of central or testicular origin. 
 
Azoospermic men with normal size testes with normal serum follicle-stimulating hormone (FSH) levels are more likely to have obstructive azoospermia, while men with a significant elevation in FSH have a testicular failure, and thus testicular NOA.

On the other hand, low gonadotropins levels with low to low-normal T points towards a diagnosis of central NOA.

According to the American Society for Reproductive Medicine (ASRM) Practice Committee, the evaluation begins with a standard reproductive history and physical examination, followed by measurement of serum FSH and testosterone(T), luteinizing hormone (LH), free T, estradiol, and prolactin. Most experts state that an FSH >7.6 mIU/mL would be considered abnormal.

Semen volume and FSH levels play an essential part in determining the etiology of azoospermia. If men have low semen volume and normal FSH the lab test should be repeated after 2-3 days of abstinence, with attention to proper collection technique. A post-ejaculate urinalysis is advised to rule out retrograde ejaculation. If there is no retrograde ejaculation and semen pH is < 7.2, a transrectal ultrasound (TRUS) is the next step to identify a possible ejaculatory duct obstruction (EDO).

In men with normal semen volume, determining serum FSH and testicular volume is critical to decide in favor of testicular biopsy for the prognostic purpose. Elevation of serum FSH along with low testicular volume strongly suggests NOA. In case sperm retrieval is planned for ICSI, the testicular biopsy is deferred till the sperm retrieval when a biopsy sample is concurrently sent to the lab.

A normal testicular biopsy indicates an obstruction at some level in the reproductive tract. If the cause of OA is not iatrogenic, then the cause is a bilateral epididymal obstruction. It should be confirmed by surgical exploration. Vasography is only indicated if reconstructive surgery is planned simultaneously.

In men with the congenital bilateral absence of the vasa deferentia (CBAVD or vasal agenesis), unilateral renal agenesis should be ruled out. Most men with vasal agenesis will also have seminal vesicle hypoplasia or agenesis which manifests as low semen volume and pH.

CBAVD is also strongly associated with mutations of the CFTR gene. Hence, before planning a sperm retrieval for ICSI in men with CBAVD or congenital unilateral absence of the vas deferens (CUAVD), genetic testing should be offered to female partner to rule out her carrier status (4%) for CFTR gene.

Men with suspected NOA due to an elevated FSH and a normal ejaculate volume have bilateral testicular atrophy.  They should be offered genetic testing to exclude chromosomal abnormalities and Y-chromosome microdeletions (YCMD). A diagnostic testicular biopsy is not usually indicated in such cases. 

Low gonadotropins levels may be because of feedback inhibition secondary to exogenous T or illicit anabolic-androgenic steroid use, a high T level with suppressed gonadotropins will be confirmatory in such instances.

In men with markedly elevated serum FSH levels, the diagnostic testicular biopsy is only indicated when there is uncertainty about the etiology of the azoospermia- obstructive or nonobstructive. In all other cases, a testicular biopsy is done when sperm retrieval is planned for ICSI.

A diagnostic biopsy is also not necessary in patients with expected obstruction and normal FSH levels.



Monday, March 19, 2018

Subclinical Hypothyroidism linked to unexplained infertility


Women with unexplained infertility (UI) were twice as likely to have a raised TSH level as compared to women who were not able to conceive because of male factor infertility reports the results of a cross-sectional study published in February issue of Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

About 10-30% of the infertile couples have unexplained infertility, defined as an inability to conceive with 12 months of unprotected intercourse with no explainable cause.

Data on the association between subclinical hypothyroidism and infertility is so far limited because of different levels of TSH cutoffs.

For this study, the Harvard based researchers looked at data from large academic health system over a period of 12 years and recruited 239 women with TSH (≤5 mIU/L) and prolactin levels (≤20 ng/ml) within normal range.  Of these women, 187 were diagnosed as UI (study arm), while in 52 women the male partner suffered from azoospermia or severely oligospermia with no other factor diagnosed for infertility (control arm).

After accounting for age, body mass index, and smoking status, it was seen that nearly 27% of women in UI group had TSH ≥2.5 mIU/L as compared to 13% in control group (P < 0.05).

The prolactin levels were comparable between both the groups.

Pouneh K. Fazeli, study’s senior author and a researcher at Massachusetts General Hospital and Harvard Medical School in Boston said, “Since our study shows that women with unexplained infertility have higher TSH levels compared to women experiencing infertility due to a known cause, more research is needed to determine whether treating these higher TSH levels with thyroid hormone can improve their chances of getting pregnant.”