TRT: fertility restoration log and questions

jd1442

New Member
Hi, first time posting - had lots of value out of these forums and read most of the stickied and recommended logs for fertility restoration following TRT. Wanted to set out where I'm up to so far and history to (hopefully) get some advice or at least perspectives from the community. Also just to set all this out, as it's not the kind of thing that's simple or understandable to discuss with friends.

History in short

40 year old guy, based in the UK. Multiple low T symptoms and low / normal T levels stretching back more than 12 years ~ 13nmol/l / 375 ng/dl. Aged 28, and perhaps fairly as a single guy hoping for fertility, NHS declined to prescribe long-term even though a short term trial of testogel did show symptom relief. Struggled on almost 10 years or so, napping during the day, little energy, good patches and bad patches. During this time I met my now wife. Conceived my 3.5 year old son first month of trying back in late 2021 and while waiting for semen analysis (had one performed as a baseline given my issues to check no problems) Ironically, the results came back low (6m total count) and we received the results the week after the pregnancy test. Pregnancy co-incided with a new job - longer hours, travel, more stress. Weighed up the pros and cons of starting TRT and decided I needed the energy to be a good Dad, make the career move work etc.
Started 50mg x 2 per week cypionate and 350iu HCG x 2 per week a few months after conceiving. Symptom releif was dramatic and has been sustained. The only thing not to fully improve has been libido, but fatigue, concentration, mood, stamina etc all great.

Where I am now

Started to trying to conceive last July to add to the family. Nothing happened for the first two months so decided to get a semen analysis (home kit) which came back at zero. Subsequent lab semen test validated that. Obivously panicking with that result despite the HCG. Can only thing a) HCG dose was insufficient b) HCG wasn't genuine (had to source myself) c) HCG alone insufficient to maintain fertility for me.
Transferred my care to a TRT specialist with interest in fertility. Initially took me off all exogenous testosterone for eight weeks with just 150iu HCG daily, Clomid 50mg every third day and 75mg HMG x 2 per week. Bloods at that two month mark revealed testosterone back at the levels I'd naturally produce at 13nmol/l / 375 ng/dl. Subjectively I did not feel good. With natural response ok, my doctor added back in 6mg Test cyp daily. Levels then at the top of the range within a month. I still didn't feel great, however. Subjectively I'd say my testicles were hanging a little lower but nothing dramatic.

Semen analyses in November and Decemeber still showed zero count. I consulted with a fertility specialist at a reproductive centre so said the HCG dose was insufficient and should have been pulsatile. He saw no resason to take me off the exogenous TRT and referred to the Larry Lipshultz research. Clomid was discontinued (he does not like it) and HCG was increased to 5000iu per week split across three doses and HMG to 75iu x 3 per week. This was 11 January. Subjectively, lots of the random joint pain and mood swings I was having have gone (assume due to dropping clomid?) Experiencing some fatigue and water weight gain but no other obvious signs of high E2. Home semen analysis performed last week still showed no sperm.

So we're now five and a half months on of adding (confirmed genuine but perhaps not at the right dose) HCG and HMG into the protocol with no results at all. I know I have been fertile in the past with the 6m count in 2021 (which I conceived my son with) and a 45m total count performed 12 years ago during initial investigations.

Current thoughts:

* Should I not have seen something by now with the regime, especially with the HMG?
* Could the exogenous Testosterone be suppressing things? Even with the LL research, it's hard not to wonder that. No desire to suffer through more months of symptoms without exogenous T, but would be willing to if that was the blocker. There do seem to be anedtoral accounts across Reddit and other forums of people who had no luck with HCG/HMG but did with Clomiphene/enclomiphene
* Is there anything else I could be adding to the protocol?

Otherwise fit and well. Normal BMI, 12% BF. Weights and cardio. Healthy diet, multivitamin, fish oil, COQ10.

Thoughts and advice gratefully received. Thank you.
 
Hi, first time posting - had lots of value out of these forums and read most of the stickied and recommended logs for fertility restoration following TRT. Wanted to set out where I'm up to so far and history to (hopefully) get some advice or at least perspectives from the community. Also just to set all this out, as it's not the kind of thing that's simple or understandable to discuss with friends.

History in short

40 year old guy, based in the UK. Multiple low T symptoms and low / normal T levels stretching back more than 12 years ~ 13nmol/l / 375 ng/dl. Aged 28, and perhaps fairly as a single guy hoping for fertility, NHS declined to prescribe long-term even though a short term trial of testogel did show symptom relief. Struggled on almost 10 years or so, napping during the day, little energy, good patches and bad patches. During this time I met my now wife. Conceived my 3.5 year old son first month of trying back in late 2021 and while waiting for semen analysis (had one performed as a baseline given my issues to check no problems) Ironically, the results came back low (6m total count) and we received the results the week after the pregnancy test. Pregnancy co-incided with a new job - longer hours, travel, more stress. Weighed up the pros and cons of starting TRT and decided I needed the energy to be a good Dad, make the career move work etc.
Started 50mg x 2 per week cypionate and 350iu HCG x 2 per week a few months after conceiving. Symptom releif was dramatic and has been sustained. The only thing not to fully improve has been libido, but fatigue, concentration, mood, stamina etc all great.

Where I am now

Started to trying to conceive last July to add to the family. Nothing happened for the first two months so decided to get a semen analysis (home kit) which came back at zero. Subsequent lab semen test validated that. Obivously panicking with that result despite the HCG. Can only thing a) HCG dose was insufficient b) HCG wasn't genuine (had to source myself) c) HCG alone insufficient to maintain fertility for me.
Transferred my care to a TRT specialist with interest in fertility. Initially took me off all exogenous testosterone for eight weeks with just 150iu HCG daily, Clomid 50mg every third day and 75mg HMG x 2 per week. Bloods at that two month mark revealed testosterone back at the levels I'd naturally produce at 13nmol/l / 375 ng/dl. Subjectively I did not feel good. With natural response ok, my doctor added back in 6mg Test cyp daily. Levels then at the top of the range within a month. I still didn't feel great, however. Subjectively I'd say my testicles were hanging a little lower but nothing dramatic.

Semen analyses in November and Decemeber still showed zero count. I consulted with a fertility specialist at a reproductive centre so said the HCG dose was insufficient and should have been pulsatile. He saw no resason to take me off the exogenous TRT and referred to the Larry Lipshultz research. Clomid was discontinued (he does not like it) and HCG was increased to 5000iu per week split across three doses and HMG to 75iu x 3 per week. This was 11 January. Subjectively, lots of the random joint pain and mood swings I was having have gone (assume due to dropping clomid?) Experiencing some fatigue and water weight gain but no other obvious signs of high E2. Home semen analysis performed last week still showed no sperm.

So we're now five and a half months on of adding (confirmed genuine but perhaps not at the right dose) HCG and HMG into the protocol with no results at all. I know I have been fertile in the past with the 6m count in 2021 (which I conceived my son with) and a 45m total count performed 12 years ago during initial investigations.

Current thoughts:

* Should I not have seen something by now with the regime, especially with the HMG?
* Could the exogenous Testosterone be suppressing things? Even with the LL research, it's hard not to wonder that. No desire to suffer through more months of symptoms without exogenous T, but would be willing to if that was the blocker. There do seem to be anedtoral accounts across Reddit and other forums of people who had no luck with HCG/HMG but did with Clomiphene/enclomiphene
* Is there anything else I could be adding to the protocol?

Otherwise fit and well. Normal BMI, 12% BF. Weights and cardio. Healthy diet, multivitamin, fish oil, COQ10.

Thoughts and advice gratefully received. Thank you.
Here's a good article for you.

 
Hi, first time posting - had lots of value out of these forums and read most of the stickied and recommended logs for fertility restoration following TRT. Wanted to set out where I'm up to so far and history to (hopefully) get some advice or at least perspectives from the community. Also just to set all this out, as it's not the kind of thing that's simple or understandable to discuss with friends.

History in short

40 year old guy, based in the UK. Multiple low T symptoms and low / normal T levels stretching back more than 12 years ~ 13nmol/l / 375 ng/dl. Aged 28, and perhaps fairly as a single guy hoping for fertility, NHS declined to prescribe long-term even though a short term trial of testogel did show symptom relief. Struggled on almost 10 years or so, napping during the day, little energy, good patches and bad patches. During this time I met my now wife. Conceived my 3.5 year old son first month of trying back in late 2021 and while waiting for semen analysis (had one performed as a baseline given my issues to check no problems) Ironically, the results came back low (6m total count) and we received the results the week after the pregnancy test. Pregnancy co-incided with a new job - longer hours, travel, more stress. Weighed up the pros and cons of starting TRT and decided I needed the energy to be a good Dad, make the career move work etc.
Started 50mg x 2 per week cypionate and 350iu HCG x 2 per week a few months after conceiving. Symptom releif was dramatic and has been sustained. The only thing not to fully improve has been libido, but fatigue, concentration, mood, stamina etc all great.

Where I am now

Started to trying to conceive last July to add to the family. Nothing happened for the first two months so decided to get a semen analysis (home kit) which came back at zero. Subsequent lab semen test validated that. Obivously panicking with that result despite the HCG. Can only thing a) HCG dose was insufficient b) HCG wasn't genuine (had to source myself) c) HCG alone insufficient to maintain fertility for me.
Transferred my care to a TRT specialist with interest in fertility. Initially took me off all exogenous testosterone for eight weeks with just 150iu HCG daily, Clomid 50mg every third day and 75mg HMG x 2 per week. Bloods at that two month mark revealed testosterone back at the levels I'd naturally produce at 13nmol/l / 375 ng/dl. Subjectively I did not feel good. With natural response ok, my doctor added back in 6mg Test cyp daily. Levels then at the top of the range within a month. I still didn't feel great, however. Subjectively I'd say my testicles were hanging a little lower but nothing dramatic.

Semen analyses in November and Decemeber still showed zero count. I consulted with a fertility specialist at a reproductive centre so said the HCG dose was insufficient and should have been pulsatile. He saw no resason to take me off the exogenous TRT and referred to the Larry Lipshultz research. Clomid was discontinued (he does not like it) and HCG was increased to 5000iu per week split across three doses and HMG to 75iu x 3 per week. This was 11 January. Subjectively, lots of the random joint pain and mood swings I was having have gone (assume due to dropping clomid?) Experiencing some fatigue and water weight gain but no other obvious signs of high E2. Home semen analysis performed last week still showed no sperm.

So we're now five and a half months on of adding (confirmed genuine but perhaps not at the right dose) HCG and HMG into the protocol with no results at all. I know I have been fertile in the past with the 6m count in 2021 (which I conceived my son with) and a 45m total count performed 12 years ago during initial investigations.

Current thoughts:

* Should I not have seen something by now with the regime, especially with the HMG?
* Could the exogenous Testosterone be suppressing things? Even with the LL research, it's hard not to wonder that. No desire to suffer through more months of symptoms without exogenous T, but would be willing to if that was the blocker. There do seem to be anedtoral accounts across Reddit and other forums of people who had no luck with HCG/HMG but did with Clomiphene/enclomiphene
* Is there anything else I could be adding to the protocol?

Otherwise fit and well. Normal BMI, 12% BF. Weights and cardio. Healthy diet, multivitamin, fish oil, COQ10.

Thoughts and advice gratefully received. Thank you.

Started 50mg x 2 per week cypionate and 350iu HCG x 2 per week a few months after conceiving. Symptom releif was dramatic and has been sustained. The only thing not to fully improve has been libido, but fatigue, concentration, mood, stamina etc all great.


You never posted labs but such dose would most likely have you hitting a healthy or high trough FT which is the critical fraction here when it comes to the positive effects.




Transferred my care to a TRT specialist with interest in fertility. Initially took me off all exogenous testosterone for eight weeks with just 150iu HCG daily, Clomid 50mg every third day and 75mg HMG x 2 per week. Bloods at that two month mark revealed testosterone back at the levels I'd naturally produce at 13nmol/l / 375 ng/dl. Subjectively I did not feel good. With natural response ok, my doctor added back in 6mg Test cyp daily. Levels then at the top of the range within a month. I still didn't feel great, however. Subjectively I'd say my testicles were hanging a little lower but nothing dramatic.


When speaking of labs always post your trough TT and more importantly FT with the reference ranges/testing method used.

Otherwise we are shooting in the dark here.

Without posting your trough TT and more importantly FT if you are hitting a TT in the top end of the reference range your FT would be a lot lower then where it sat on your original protocol 100 mg T/week split into twice-weekly injections as your current protocol 42 mg T/week split 6 mg daily is not a high dose.

Even then if you have high SHBG which will inflate the TT your FT may not be high enough although it would still be. healthy unless you had very high SHBG.

Most men on T-therapy are injecting 100-200 mg T/week whether once weekly or split into more frequent injections.

The majority of men can easily hit a. healthy/high trough FT injecting 100-150 mg T/week especially when split into more frequent injections.

There will always be those outliers who may need the higher-end dose 200 mg T/week but it is far from common as in rare.

Such dose would be overkill for the majority of men on therapy.

On the other end of the spectrum there are some who can achieve stellar levels injecting <100 mg T/week especially when split into more frequent injections but most doctors in the know would not go below 60 mg T/week.

The standard starting dose across the board by those in the know is 100 mg T/week or 50 mg T twice-weekly.




Semen analyses in November and Decemeber still showed zero count. I consulted with a fertility specialist at a reproductive centre so said the HCG dose was insufficient and should have been pulsatile. He saw no resason to take me off the exogenous TRT and referred to the Larry Lipshultz research. Clomid was discontinued (he does not like it) and HCG was increased to 5000iu per week split across three doses and HMG to 75iu x 3 per week. This was 11 January. Subjectively, lots of the random joint pain and mood swings I was having have gone (assume due to dropping clomid?) Experiencing some fatigue and water weight gain but no other obvious signs of high E2. Home semen analysis performed last week still showed no sperm.

So we're now five and a half months on of adding (confirmed genuine but perhaps not at the right dose) HCG and HMG into the protocol with no results at all. I know I have been fertile in the past with the 6m count in 2021 (which I conceived my son with) and a 45m total count performed 12 years ago during initial investigations.



You easily have room to increase your weekly dose of hCG and hMG.

May need 3000IU hCG and 150IU hMG 3 x/week and in some cases up to 400IU.

Although hCG is needed for maintaining ITT (intratesticuar testosterone) when it comes to fertility/sperm production the addition of FSH is critical in many cases.

Would definitely up your weekly doses before throwing in the towel here.

Worst case scenario would be coming off T and restarting mono-therapy.




Look over the threads in post #5 which is stacked with numerous papers/studies.

All of the most recent Lipshultz studies to boot!





 
Hi, first time posting - had lots of value out of these forums and read most of the stickied and recommended logs for fertility restoration following TRT. Wanted to set out where I'm up to so far and history to (hopefully) get some advice or at least perspectives from the community. Also just to set all this out, as it's not the kind of thing that's simple or understandable to discuss with friends.

History in short

40 year old guy, based in the UK. Multiple low T symptoms and low / normal T levels stretching back more than 12 years ~ 13nmol/l / 375 ng/dl. Aged 28, and perhaps fairly as a single guy hoping for fertility, NHS declined to prescribe long-term even though a short term trial of testogel did show symptom relief. Struggled on almost 10 years or so, napping during the day, little energy, good patches and bad patches. During this time I met my now wife. Conceived my 3.5 year old son first month of trying back in late 2021 and while waiting for semen analysis (had one performed as a baseline given my issues to check no problems) Ironically, the results came back low (6m total count) and we received the results the week after the pregnancy test. Pregnancy co-incided with a new job - longer hours, travel, more stress. Weighed up the pros and cons of starting TRT and decided I needed the energy to be a good Dad, make the career move work etc.
Started 50mg x 2 per week cypionate and 350iu HCG x 2 per week a few months after conceiving. Symptom releif was dramatic and has been sustained. The only thing not to fully improve has been libido, but fatigue, concentration, mood, stamina etc all great.

Where I am now

Started to trying to conceive last July to add to the family. Nothing happened for the first two months so decided to get a semen analysis (home kit) which came back at zero. Subsequent lab semen test validated that. Obivously panicking with that result despite the HCG. Can only thing a) HCG dose was insufficient b) HCG wasn't genuine (had to source myself) c) HCG alone insufficient to maintain fertility for me.
Transferred my care to a TRT specialist with interest in fertility. Initially took me off all exogenous testosterone for eight weeks with just 150iu HCG daily, Clomid 50mg every third day and 75mg HMG x 2 per week. Bloods at that two month mark revealed testosterone back at the levels I'd naturally produce at 13nmol/l / 375 ng/dl. Subjectively I did not feel good. With natural response ok, my doctor added back in 6mg Test cyp daily. Levels then at the top of the range within a month. I still didn't feel great, however. Subjectively I'd say my testicles were hanging a little lower but nothing dramatic.

Semen analyses in November and Decemeber still showed zero count. I consulted with a fertility specialist at a reproductive centre so said the HCG dose was insufficient and should have been pulsatile. He saw no resason to take me off the exogenous TRT and referred to the Larry Lipshultz research. Clomid was discontinued (he does not like it) and HCG was increased to 5000iu per week split across three doses and HMG to 75iu x 3 per week. This was 11 January. Subjectively, lots of the random joint pain and mood swings I was having have gone (assume due to dropping clomid?) Experiencing some fatigue and water weight gain but no other obvious signs of high E2. Home semen analysis performed last week still showed no sperm.

So we're now five and a half months on of adding (confirmed genuine but perhaps not at the right dose) HCG and HMG into the protocol with no results at all. I know I have been fertile in the past with the 6m count in 2021 (which I conceived my son with) and a 45m total count performed 12 years ago during initial investigations.

Current thoughts:

* Should I not have seen something by now with the regime, especially with the HMG?
* Could the exogenous Testosterone be suppressing things? Even with the LL research, it's hard not to wonder that. No desire to suffer through more months of symptoms without exogenous T, but would be willing to if that was the blocker. There do seem to be anedtoral accounts across Reddit and other forums of people who had no luck with HCG/HMG but did with Clomiphene/enclomiphene
* Is there anything else I could be adding to the protocol?

Otherwise fit and well. Normal BMI, 12% BF. Weights and cardio. Healthy diet, multivitamin, fish oil, COQ10.

Thoughts and advice gratefully received. Thank you.

Some key points. here!

. Patients with larger testicular volumes, higher starting sperm concentrations, and lower serum FSH levels were more likely to respond to hCG/FSH reboot. Patient age and prior testosterone therapy duration did not predict therapy success contrary to previous studies (19).








* We stratified the entire cohort into two groups: those not on concurrent testosterone therapy during hCG/FSH reboot (No testosterone therapy) vs. those who were (Concurrent testosterone therapy). Although testosterone dosing was not standardized within this latter cohort, all patients were undergoing 100 mg-400 mg of injectable testosterone therapy per week.

* We conducted a retrospective cohort analysis of men prescribed 3000 International Units (IU) of hCG and 75IU of FSH three times a week (self-administered by subcutaneous injection) who sought infertility treatment at a single andrology clinic at Baylor College of Medicine from January 2020-March 2024. We termed this therapy “hCG/FSH reboot”. All patients received these medications from a single local compounding pharmacy with approved access to purified (i.e. non-recombinant) preparations of hCG and FSH. To promote patient compliance and not deviate from the standard three times a week dosing of hCG monotherapy, all patients were instructed to draw up both the hCG and FSH into the same syringe and inject both agents via one injection on Mondays, Wednesdays, and Fridays.


* Three-quarters of infertile men with prior testosterone therapy demonstrated sperm concentration improvements after hCG/FSH reboot. Concurrent use of testosterone therapy did not dampen hCG/FSH-mediated spermatogenic recovery. Patients with larger testicular volumes, higher starting sperm concentrations, and lower serum FSH levels were more likely to respond to hCG/FSH reboot. Patient age and prior testosterone therapy duration did not predict therapy success contrary to previous studies (19).


* Interestingly, work by Roth demonstrates that far lower doses of hCG than those used clinically (just 125 IU of hCG every other day for 5 days) can adequately restore intratesticular testosterone levels required for spermatogenesis (21). Perhaps current hCG treatment regimens are supratherapeutic. Fortunately, reported side effects of hCG are minimal (22,23). Conversely, dosing oligospermic men with the 75 IU of FSH three times a week employed in this study may be subtherapeutic. A meta-analysis by Canarella assessed the efficacy of FSH dosing in men with idiopathic oligospermia and grouped dosing regimens into low (175-262.5 IU/week), intermediate (350-525 IU/week), and high (700-1050 IU/week) (24). Those on the low-dosing regimen demonstrated improvements only in sperm motility. Those on the high-dosing regimen demonstrated increases in sperm concentration, total sperm count, and motility.

* In our patient cohort of severely oligospermic men undergoing hCG/FSH, we found that 58% of these patients returned to normospermia. Our findings may support that hCG/FSH is a superior treatment regimen for the recovery of spermatogenesis in infertile men with a history of testosterone use.

* Optimal dosing of hCG and FSH for male factor fertility remains to be determined




 
Thank you both for taking the time to reply. Madman, I'd not seen that study discussing therapeutic doses of FSH. I had not considered 75iu X3 per week may be too low.

My TRT clinic's rationale with the 6mg daily / 42mg per week was to 'top up' the endogenous testosteorne my testes were producing when just on the HCG, Clomid and HMG. Subjectively I felt ok (albeit not amazing) on that protocol - just no sperm at the four month mark.

Now six weeks into the updated protocol from my fertility consultant, and almost six months since this all began, and I'm not feeling as good. Random aches and pains everywhere, mood is up and down, and I've gained 8lbs with no change in diet.

Just had bloods drawn yesterday in the morning, before injecting any of my medication. E2 elevated so I assume that is causing the negative symptoms.

Albumin: 38 g/L (Range: 35 - 50) - Normal
SHBG: 17 nmol/L (Range: 18.3 - 54.1) - Low
FSH: 2.8 IU/L (Range: 1.5 - 12.4) - Normal
LH: <0.3 IU/L (Range: 1.7 - 8.6) - Low
Oestradiol: 218 pmol/L (Range: 41 - 159) - High
Testosterone: 29.80 nmol/L (Range: 12 - 30) - Normal (Normal)
Free Testosterone: 1.013 nmol/L (Range: 0.2 - 0.62) - High
Free Androgen Index: 174.3 (Range: 24 - 104) - High
Prolactin: 367 mIU/L (Range: 86 - 324) - High
DHEA Sulphate: 5.72 umol/L (Range: 2.41 - 11.6) - Normal

I have a repeat sperm analysis next Friday and plan to email the blood results to the consultant.


I think my questions / thought process now are:

* Can the E2 be managed with arimidex to bring it down?

* Would he consider increasing the HMG /FSH dosing to the higher end in that study ~1000iu weekly? (A concern there would be cost to be honest, if that was required for months)

* Would he adjust anything now or wait for one full sperm maturation cycle on the increased HCG dose (74 days)?

* When, if at all, would he consider switching to CC/EC monotherapy, if at all?

A question for everyone here: has anyone had any success with micro tese despite zero sperm in the ejaculate? The literature seems to indicate a roughly 50% success rate. When we discussed briefly with my consultant he thought six months was too ealry to be considering that.
 
Thank you both for taking the time to reply. Madman, I'd not seen that study discussing therapeutic doses of FSH. I had not considered 75iu X3 per week may be too low.

My TRT clinic's rationale with the 6mg daily / 42mg per week was to 'top up' the endogenous testosteorne my testes were producing when just on the HCG, Clomid and HMG. Subjectively I felt ok (albeit not amazing) on that protocol - just no sperm at the four month mark.

Now six weeks into the updated protocol from my fertility consultant, and almost six months since this all began, and I'm not feeling as good. Random aches and pains everywhere, mood is up and down, and I've gained 8lbs with no change in diet.

Just had bloods drawn yesterday in the morning, before injecting any of my medication. E2 elevated so I assume that is causing the negative symptoms.

Albumin: 38 g/L (Range: 35 - 50) - Normal
SHBG: 17 nmol/L (Range: 18.3 - 54.1) - Low
FSH: 2.8 IU/L (Range: 1.5 - 12.4) - Normal
LH: <0.3 IU/L (Range: 1.7 - 8.6) - Low
Oestradiol: 218 pmol/L (Range: 41 - 159) - High
Testosterone: 29.80 nmol/L (Range: 12 - 30) - Normal (Normal)
Free Testosterone: 1.013 nmol/L (Range: 0.2 - 0.62) - High
Free Androgen Index: 174.3 (Range: 24 - 104) - High
Prolactin: 367 mIU/L (Range: 86 - 324) - High
DHEA Sulphate: 5.72 umol/L (Range: 2.41 - 11.6) - Normal

I have a repeat sperm analysis next Friday and plan to email the blood results to the consultant.


I think my questions / thought process now are:

* Can the E2 be managed with arimidex to bring it down?

* Would he consider increasing the HMG /FSH dosing to the higher end in that study ~1000iu weekly? (A concern there would be cost to be honest, if that was required for months)

* Would he adjust anything now or wait for one full sperm maturation cycle on the increased HCG dose (74 days)?

* When, if at all, would he consider switching to CC/EC monotherapy, if at all?

A question for everyone here: has anyone had any success with micro tese despite zero sperm in the ejaculate? The literature seems to indicate a roughly 50% success rate. When we discussed briefly with my consultant he thought six months was too ealry to be considering that.

Now six weeks into the updated protocol from my fertility consultant, and almost six months since this all began, and I'm not feeling as good. Random aches and pains everywhere, mood is up and down, and I've gained 8lbs with no change in diet.

Just had bloods drawn yesterday in the morning, before injecting any of my medication. E2 elevated so I assume that is causing the negative symptoms.

Albumin: 38 g/L (Range: 35 - 50) - Normal
SHBG: 17 nmol/L (Range: 18.3 - 54.1) - Low
FSH: 2.8 IU/L (Range: 1.5 - 12.4) - Normal
LH: <0.3 IU/L (Range: 1.7 - 8.6) - Low
Oestradiol: 218 pmol/L (Range: 41 - 159) - High
Testosterone: 29.80 nmol/L (Range: 12 - 30) - Normal (Normal)
Free Testosterone: 1.013 nmol/L (Range: 0.2 - 0.62) - High

Free Androgen Index: 174.3 (Range: 24 - 104) - High
Prolactin: 367 mIU/L (Range: 86 - 324) - High
DHEA Sulphate: 5.72 umol/L (Range: 2.41 - 11.6) - Normal



As you can see on your current protocol hCG (5000IU 3X weekly) + hMG (75IU 3x weekly) you are hitting a high-end TT 859.5 ng/dL and with a low SHBG 17 nmol/L it is a given that your FT would be high as it is well over the top-end of the reference range.

You never posted the testing method but it was most likely calculated although it is not using the go to linear law-of-mass action Vermeulen (cFTV).

If we calculated your FT using the go to cFTV with a high-end TT 859.5 ng/dL, low SHBG 17 nmol/L and Albumin 3.8 g/dL then your FT 29.5 ng/dL is very high!



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This is why your estradiol is high and even then use hCG will have a big impact on driving up estradiol/prolactin.

Not only is your estradiol elevated but your prolactin is also high which can easily dampen ones libido and mood.

LH would be low as expected when using hCG mono therapy since your HPG-axis is shut-down.

No need to test FAI as it is a useless marker, free testosterone is what truly matters here.

The 8lbs you packed on would be mostly bloat/water retention which can be common when using hCG especially high doses.




Now six weeks into the updated protocol from my fertility consultant,
I have a repeat sperm analysis next Friday and plan to email the blood results to the consultant.


You are only six weeks in so there is no point in repeating the SA as you would need to wait 3 months since it will take roughly 68-72 days to make new sperm.




I think my questions / thought process now are:
* Can the E2 be managed with arimidex to bring it down?


Yes as this can be standard practice in such cases but you need to be mindful of the dose used as many will fare much better micro-dosing to avoid crashing estradiol as the goal would be to bring it down but keep it in a healthy range as healthy estradiol is critical to men's health.

* An aromatase inhibitor is prescribed of-label if the estradiol (E2) levels exceed 50 pg/mL or if the TT (ng/dL) to E2 (pg/mL) ratio (T/E2 ratio) falls below 10. The aromatase inhibitor is given orally (e.g., anastrozole, 1 mg daily) to keep the estradiol levels below 50 pg/mL and the T/E2 ratio above 10.




Fig. 3 The Esteves gonadotropin treatment protocol for infertile males with non-obstructive azoospermia and hypogonadism.
The treatment involves the off-label use of human chorionic gonadotropin (hCG) alone or in combination with follicle-stimulating hormone (FSH). Given the off-label nature of the treatment, patients must provide signed informed consent before initiating therapy. Subcutaneous injections of choriogonadotropin alfa (recombinant human chorionic gonadotropin [rhCG], 250 μg/0.5 mL pre-flilled pen for injection) in doses of 80 μg (~2080 IU), are self-administered twice weekly. The dose is adjusted to keep the total testosterone (TT) level >350 and up to 900 ng/dL. If the serum FSH level falls below 1.5 IU/L during rhCG stimulation, patients are also given recombinant FSH (follitropin alfa [rFSH], 300 IU/0.5 mL, using a pre-filled multidose pen ready for injection). The rFSH is administered at a dose of 150–225 IU two (biw) to three (tiw) times a week, concurrent to the rhCG therapy, for at least 3 months. An aromatase inhibitor is prescribed of-label if the estradiol (E2) levels exceed 50 pg/mL or if the TT (ng/dL) to E2 (pg/mL) ratio (T/E2 ratio) falls below 10. The aromatase inhibitor is given orally (e.g., anastrozole, 1 mg daily) to keep the estradiol levels below 50 pg/mL and the T/E2 ratio above 10.





* Would he consider increasing the HMG /FSH dosing to the higher end in that study ~1000iu weekly? (A concern there would be cost to be honest, if that was required for months)


Yes if he is up to date on the literature those in the know would increase the dose 75IU--->150IU and in some cases up to 400IU before throwing in the towel.

Again you would easily have room to increase the weekly hCG dose too.




* Would he adjust anything now or wait for one full sperm maturation cycle on the increased HCG dose (74 days)?

No this would not be a smart move as complete recovery of spermatogenesis would take 3 months due to the life cycle.




* When, if at all, would he consider switching to CC/EC monotherapy, if at all?

If higher doses of hCG/hMG do not improve your situation then he would need to look at other options especially as some men will not respond well even when following a longer-term >3 month protocol.

Worst case scenario micro-tese.

Look over the most recent Lipshultz study.

Some key point here!


* Accordingly, one should not generalize our findings and propose that hCG/FSH therapy would benefit all infertile male patients.

* Our study is also limited by its relatively short follow-up. Although the median time on hCG/FSH reboot to achieve the highest documented sperm concentration was 4.7 months, the upper quartile of therapy duration ranged from 8.7 to 29.4 months. Within this upper quartile, however, 73% of patients still demonstrated an improvement in their sperm concentrations vs. 74% of patients in the lower three quartiles. This raises the possibility that some patients may take longer to respond to hCG/FSH reboot therapy.




The inherent limitation of our study is its retrospective nature without strict inclusion criteria, randomization, or patient monitoring (i.e., some data, such as hormone levels, are not completely captured). Specific limitations and selection biases also include the following: 1) exclusion of patients not undergoing a subsequent semen analysis after initial prescription of hCG/FSH therapy (n=102, potentially missing those patients unable to afford the high cost of hCG/FSH), 2) exclusion of patients without a documented history of testosterone use (n=39, raising the question of whether hCG/FSH therapy would benefit testosterone naïve infertile patients), and 3) exclusion of patients documented to be normospermic (>15 M/mL) despite being treated for infertility (n=8, highlighting whether gonadotropic therapy could improve not only sperm quantity but quality). Accordingly, one should not generalize our findings and propose that hCG/FSH therapy would benefit all infertile male patients.

Our study is also limited by its relatively short follow-up. Although the median time on hCG/FSH reboot to achieve the highest documented sperm concentration was 4.7 months, the upper quartile of therapy duration ranged from 8.7 to 29.4 months. Within this upper quartile, however, 73% of patients still demonstrated an improvement in their sperm concentrations vs. 74% of patients in the lower three quartiles. This raises the possibility that some patients may take longer to respond to hCG/FSH reboot therapy. Longer follow-up will be required to better understand this regimen’s safety and efficacy profile. Finally, we did not assess fertility outcomes in patients undergoing hCG/FSH reboot therapy as our IRB did not include calling patients for follow up. However, men with isolated hypogonadotropic hypogonadism treated with human Menopausal Gonadotropin ,a combination of urinary purified LH and FSH, can reliably achieve pregnancy despite having severe oligospermia or oligospermia(31). Thus, we posit that any improvement in sperm concentration secondary to hCG/FSH therapy represents a means to restore fertility in men with prior testosterone use.

Key to implementing standardized, guideline-based treatment protocols for the treatment of infertility secondary to testosterone use are prospective trials. To confirm these data, the authors are currently designing a multi-center, randomized, and controlled trial to assess hCG/FSH therapy in infertile men with prior testosterone use. Studies of importance should also include prospective trials comparing the efficacy of hCG monotherapy or hCG/Clomiphene to hCG/FSH, as well as the efficacy of hCG/FSH therapy in testosterone naïve patients(18).

Ultimately, the strength of this study is its size, representing the largest study to date investigating the utility of gonadotropic hCG/FSH therapy in restoring spermatogenesis in men with a history of testosterone use. Subjects followed a consistent medication regimen throughout the study, allowing appropriate analyses with semen analyses and hormonal testing at 3-month intervals. With hope of increased availability and reduced cost, hCG/FSH gonadotropic therapy may represent the optimal regimen for spermatogenic recovery in infertile men with a history of testosterone use











Fig. 3 The Esteves gonadotropin treatment protocol for infertile males with non-obstructive azoospermia and hypogonadism. The treatment involves the off-label use of human chorionic gonadotropin (hCG) alone or in combination with follicle-stimulating hormone (FSH). Given the off-label nature of the treatment, patients must provide signed informed consent before initiating therapy. Subcutaneous injections of choriogonadotropin alfa (recombinant human chorionic gonadotropin [rhCG], 250 μg/0.5 mL pre-flilled pen for injection) in doses of 80 μg (~2080 IU), are self-administered twice weekly. The dose is adjusted to keep the total testosterone (TT) level >350 and up to 900 ng/dL. If the serum FSH level falls below 1.5 IU/L during rhCG stimulation, patients are also given recombinant FSH (follitropin alfa [rFSH], 300 IU/0.5 mL, using a pre-filled multidose pen ready for injection). The rFSH is administered at a dose of 150–225 IU two (biw) to three (tiw) times a week, concurrent to the rhCG therapy, for at least 3 months. An aromatase inhibitor is prescribed of-label if the estradiol (E2) levels exceed 50 pg/mL or if the TT (ng/dL) to E2 (pg/mL) ratio (T/E2 ratio) falls below 10. The aromatase inhibitor is given orally (e.g., anastrozole, 1 mg daily) to keep the estradiol levels below 50 pg/mL and the T/E2 ratio above 10. Patients are monitored with hormone measurements (serum FSH, luteinizing hormone [LH], E2, TT, free testosterone, and 17-hydroxy-progesterone [17-OH-P]) and liver enzyme measurements for those taking aromatase inhibitors every 3–4 weeks. Semen analysis is carried out 3 months after starting the treatment and then every 4 weeks for patients who continue therapy for>3 months. If viable sperm are found in any semen analysis during treatment, sperm cryopreservation is carried out. If not, patients undergo microdissection testicular sperm extraction (micro-TESE) after ≥3 months of treatment. ICSI, intracytoplasmic sperm injection; qd, once daily. Adapted with permission from Elsevier from Esteves SC, Achermann APP, Miyaoka R, Verza S Jr, Fregonesi A, Riccetto CLZ. Clinical factors impacting microdissection testicular sperm extraction success in hypogonadal men with nonobstructive azoospermia. Fertil Steril. 2024 Jun 22: S0015-0282 (24) 00544–2. Redirecting.

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1771688791833.webp




 
Thank you both for taking the time to reply. Madman, I'd not seen that study discussing therapeutic doses of FSH. I had not considered 75iu X3 per week may be too low.

My TRT clinic's rationale with the 6mg daily / 42mg per week was to 'top up' the endogenous testosteorne my testes were producing when just on the HCG, Clomid and HMG. Subjectively I felt ok (albeit not amazing) on that protocol - just no sperm at the four month mark.

Now six weeks into the updated protocol from my fertility consultant, and almost six months since this all began, and I'm not feeling as good. Random aches and pains everywhere, mood is up and down, and I've gained 8lbs with no change in diet.

Just had bloods drawn yesterday in the morning, before injecting any of my medication. E2 elevated so I assume that is causing the negative symptoms.

Albumin: 38 g/L (Range: 35 - 50) - Normal
SHBG: 17 nmol/L (Range: 18.3 - 54.1) - Low
FSH: 2.8 IU/L (Range: 1.5 - 12.4) - Normal
LH: <0.3 IU/L (Range: 1.7 - 8.6) - Low
Oestradiol: 218 pmol/L (Range: 41 - 159) - High
Testosterone: 29.80 nmol/L (Range: 12 - 30) - Normal (Normal)
Free Testosterone: 1.013 nmol/L (Range: 0.2 - 0.62) - High
Free Androgen Index: 174.3 (Range: 24 - 104) - High
Prolactin: 367 mIU/L (Range: 86 - 324) - High
DHEA Sulphate: 5.72 umol/L (Range: 2.41 - 11.6) - Normal

I have a repeat sperm analysis next Friday and plan to email the blood results to the consultant.


I think my questions / thought process now are:

* Can the E2 be managed with arimidex to bring it down?

* Would he consider increasing the HMG /FSH dosing to the higher end in that study ~1000iu weekly? (A concern there would be cost to be honest, if that was required for months)

* Would he adjust anything now or wait for one full sperm maturation cycle on the increased HCG dose (74 days)?

* When, if at all, would he consider switching to CC/EC monotherapy, if at all?

A question for everyone here: has anyone had any success with micro tese despite zero sperm in the ejaculate? The literature seems to indicate a roughly 50% success rate. When we discussed briefly with my consultant he thought six months was too ealry to be considering that.

In this insightful podcast, they discuss:


* The challenges of treating azoospermia and oligospermia

* Why donor sperm is banned in Dubai

* How Micro TESE is revolutionizing male infertility care

* Key differences in clinical practices between India, Dubai, and the US

* Awareness, accessibility, and training of microsurgical procedures in India

* What patients should know before undergoing Micro TESE















 

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