Credits

• Section Writer: Dr. Om J Lakhani
• Section Editor: Dr. Om J Lakhani

**Induction of fertility in males with secondary hypogonadism **

Q. What are the factor that influences fertility in males with secondary hypogonadism?

• Bilateral cryptorchidism or unilateral – with no spontaneous descent my one year – reduces the chances
• Larger the size, of testis-better the response
• Hypo hypo after puberty have a better response than those before puberty
• Partial hypogonadism – better response than complete hypogonadism
• Prior treatment with Testosterone reduces chances for fertility

**Gonadotropin therapy **

Q. Describe the current protocol used for management of fertility using gonadotropins for patients with hypogonadotropic hypogonadism at Zydus hospital

• Baseline assessment
  • Testicular volume
  • SPL
  • FSH
  • LH
  • Testosterone
  • Inhibin B
  • Bone age
• If TV < 4 ml with/without Inhibin B <60 pg/ml +/- Cryptorchidism
  • Start with HMG 150 IU three times a week
  • After 2 months
    • Repeat Inhibin B
    • FSH
  • If FSH 4-8 IU/l , TV >4 ml has improved, and Inhibin B is >60 pg/ml, then add HCG
  • If the patient has symptoms of Hypogonadism- Testosterone may be temporarily added
• If TV >4 ml / Acquired hypogonadism , Inhibin B >60 , No cryptorchidism
  • Start with HCG 1500 IU twice a week and HMG 75 IU twice a week
  • Add Letrozole 2.5 mg daily
  • After 6 weeks
    • TV
    • FSH
    • Testosterone - done on day 4 after last HCG dose - repeat every 6 weeks till in normal range
    • Hemoglobin
  • Titrate the dose of HCG to achieve
    • Normal T levels
    • No Erythrocytosis
  • Titrate HMG to achieve
    • FSH value of 4-8 IU/ml
• When to take semen analysis
  • Start Semen analysis once the TV is 8 ml
  • After 2-3 days of abstinence
  • Repeat every 2-3 weeks
  • Once sperm count is good, consider cryopreservation of sperm, after which the patient may be shifted to HCG alone

Q. Can LH/HCG alone stimulate spermatogenesis?

• It often does due to improvement in intratesticular testosterone

Q. Is recombinant LH better than HCG?

• No
• HCG is good enough
• Recombinant LH has a shorter half-life than HCG and hence needs to be given daily
• Also, it is more expensive

Q. How is HCG given- subcutaneously or intramuscularly?

• It is recommended to be used IM
• However, it can be given subcutaneously (though not approved for this route)

Q. What is the starting dose for HCG?

• 1500-2000 IU intramuscularly twice/three times a week – Mon, Wed, Friday

Q. How is monitoring done with HCG treatment?

• Testosterone is measured every 1-2 months
• It is kept in the range of 400-800 ng/dl
• If this range is not achieved, increased the dose of HCG
• If dose >10,000 IU- 3 times a week –then think of anti HCG antibodies

Q. When to start measuring the sperm count?

• Sperm count is measured after testosterone has been in the normal range of 400-800 ng/dl
• Semen analysis can be done every 1-2 months
• However, semen analysis must not be used to determine response to therapy

Q. How much sperm count do we target?

• 5-10 million / ml

Q. How much time does it take to achieve this sperm count?

• 6 months  - 24 months!

Q. When is HMG / FSH added?

• If the sperm count is <5 million/ml even though testosterone has been normal for >6months
• Then add HMG/FSH
• Recently, experts recommend starting FSH/HMG early

Q. FSH is required for initiation or maintenance of spermatogenesis?

• Spermatogenesis is initiated by FSH but probably not required for maintenance

Q. How does FSH impact spermatogenesis?

• It impacts spermatogenesis via its action of Sertoli cells

Q. What is the starting dose of HMG used?

• 75 Units three times a week – can be given in the same syringe as HCG

Q. How is monitoring done once on HMG?

• Monitor Sperm count every 1-2 months
• Sperm counts fluctuate, so look for a trend

Q. When is the dose of HMG increased?

• It is increased to 150 units if the sperm count remains <5 million/ml after 6 months

Q.. Is it worthwhile to continue HCG / HMG if sperm counts are a few million?

• Yes
• Sometimes, this low value can also lead to impregnation

Q. What is the advantage of Recombinant FSH (rhFSH)?

• It is mainly developed for ovulation induction and offers no particular advantage to the patient
• It has not been head-on compared with HMG, but  extra purity of FSH may not be particularly required

Q. What is the meantime to achieving normal sperm count and fertility?

• Mean to first sperm is 7.1 month
• Mean to fertility is 28 months!

Q. When is ART considered?

• When pregnancy is not achieved within 12-24 months, ART must be considered
• Options are Intrauterine insemination, IVF or ICSI (last option)

Q. What is done once fertility is achieved?

• HCG and HMG are continued till 1st trimester of pregnancy
• After delivery, if the couple plan to conceive again, HCG is continued, and HMG is added when pregnancy is planned
• If pregnancy is not planned again  - then shift to testosterone or continue HCG

Q. What is done for cryptorchidism in CHH patients in infancy?

• Surgery is done between 6-12 months of age

Q. What is done for the micropenis?

• Testosterone, DHT, or FSH/LH between 1-6 months of age

Q. Can FSH given during infancy induce spermatogenesis?

• No
• It cannot
• Because Sertoli cells are not affected as they do not have androgen receptors in childhood
• Androgen receptors of Sertoli cells develop after five years of age

Q. How is testosterone therapy initiated or maintained in a child with hypo hypo?

• Start with a low dose of 50 mg
• Gradually increase to full adult dose over 2 years

Q. A child on testosterone therapy has an increase in the size of the testis. What does it indicate?

• Testosterone does not increase the size of the testis
• So, if the testis size has increased, it suggests a spontaneous reversal of the disease and hence stop testosterone and re-evaluate the HPG axis

Q. Describe the GnRH pump therapy

• GnRH is administered 24 hours a day (even during sleeping and bathing) at 90-minute intervals through a pump with a needle, which is introduced under the skin of the abdomen (subcutaneous). The pump can also be attached via a thin hose into a vein in the lower arm (intravenous). The pump is the most significant disadvantage of the treatment.

Q. Give the protocol for GnRH administration?

• It is injected using a pump
• IV is preferred to subcutaneous
• A pulse is given every 60-90 min
• Dose is 2.5-5 mcg per pulse