Medical treatment of male and female infertility by Dr Akram Shalabi

1. Medical Treatment of Male
and
Female Infertility
Dr. Akram H, Shalabi
Senior Consultant ObGyn
&
Reproductive Medicine
drakram_ivf@yahoo.com
+962795553199

2. Medical Treatment of Male
Infertility
 Many known causes of male infertility are treatable medically with
high success rate although the majority is idiopathic ( unexplained
OATS or azospermia )
 Rx of idiopathic / genetic male infertility is typically empirical
 understanding the HPG axis and estrogen effect is essential for Rx
through focusing on optimizing T production ( Leydig Cs ),
increasing FSH levels to stimulate Sertoli cells & spermatogenesis &
normalizing T/Estrogen ratio
 Testo & other androgens have contraceptive properties despite the
need fort T for spermatogenesis ,so they should be avoided

3. Hormonal Treatment
 GnRH : pulsatile GnRH administration is effective in HH ( Kalman’s ,
Idiopathic HH ) as it stimulates release of Gns from pituitary gland &
restores HPG pathway
Dose : 5-20µg q 1-2 hrs SC for 4 months at least
 Induces spermatogenesis in 85% of males and
60% of couples achieve pregnancy within 9-24 months
liu et al J Clin Endocrinol Meatb
Butcher et al Eur J endocrinol 1998
 Positive predictors of Rx : normal T , Gn and inhibin B levels, maturation
of SS characteristics , increased testicular size and absence of
cryptorchidism . Pettiloud et al 2002
 Hypothalamus continues GnRH secretion after Rx being withheld for a
short period of time Raivio N Engl J Med 2007

4.  Gonadotrophins : in Pituitary insufficiency ( adenoma,
hemochromatosis, sarcoidosis )
 Initially hCG is given . If no sperm is detected but adequate
serum T levels Warne DW etal. F&S 2009
Then FSH is introduced in doses of 75-150 IU 2-3 times weekly +
1500-2500 IU hCG twice weekly for 6-24 months / until sperm
appear in the ejaculate.
Gns induce spermatogenesis in 85-94 % of men
Buegues et al. H R 1997 , Miyagawa et al J Urol 2005
PR varies between 38 to 51% Liu et al, Burris et al
Gns in idiopathic OATS & non-obstructive azoospermia showed
no benefit Knuth et al. , Kamischke et al.

5.  Dopamine Agonist: in PRL secreting adenomas , not in
hyperprolactinemia induced by tumors causing stalk
compression
 Cabergoline is more effective than bromocriptine in
suppressing PRL production
Webster et al Clin endocrinol 1992
Verlhest et al J Clin Endocrinol Metab 1999
Dose 125-1000µg twice weekly
Dopamine resistance is likely if patients fail to achieve normal
PRL level or experience less than 50% reduction in adenoma size
or fail to restore fertility
In this case dose modification before surgery is recommended
Melmed et al J Clin Endocrinol Metab 2011

6.  Aromatase inhibitors AIs
anastrozole 1 mg /d or letrozole 2,5mg /d increase T/E ratio ( normal
<10:1) reducing the estrogenic effect on spermatogenesis and
inhibition of HPG axis
Candidates for AIs are males with T< 300ng/dl and T/E > 10
Pavlovich et al J Urpl 2001
Letrozole: 20% of oligospermic men achieved pregnancy & 24% of
azoospermic men had sperm in ejacultes Saylam et al F & S 2011
AIs seem to be effective in restoring LH,FSH & T levels improving
semen parameters and re-establishing infertility
Side effects of AIs include
nausia decreased libido
elevated liver enzymes decreased bone mineral density
increased total body fat Finkelstein et al N Engl J Med
2013

7.  SERMs : Selective estrogen receptor modulators ( CC,
tamoxifene, toremifene, raloxifene )
Inhibit central E feedback & up-regulate LH, FSH production leading
to induction of spermatogenesis
 In 42 males with NOA ( excluding SCS) treated with CC ( titrated to
T level of 600ng/dl)
64 % had sperm sufficient for ICSI Hussein et al. J Androl 2005
 Tamoxifene 20mg /d, Toremefine and raloxifene 60mg/d for 3/12
 Slight increase in PR 15.4% vs 12,5% in OATS , so the authors did
not support their use
MA& SR Vandekerckhove et al. 2000, Willets et al. Reprod Sci 2013

8. Antioxidants
 Men with increased ROS in seminal fluid are prone to infertility
mainly due to sperm dysfunction , germ cell DNA damage
Sharma et al Urol 1996
 No convincing trials have demonstrated a significantly higher
unassisted pregnancy rate after antioxidant therapy
Saleh et al J Andriol 2002
 Certain category of men might benefit from Anti ox Rx, yet they are
not clearly defined due to lack of RCTs

9. ‫القطب‬ ‫شوكة‬
(
‫الجريس‬
)

12. ‫المعبد‬ ‫شجرة‬
(
‫معبلة‬
)

15. ‫البوشو‬

16. ‫االرث‬ Milk Thistle / Silymarin

17. ‫السرنوة‬
(
‫النخلة‬
‫المنشارية‬
)

18. ‫النفل‬
(
‫البرسيم‬
‫االحمر‬
)

19. Combinations of Vit E &C, did not improve semen parameters despite
a meaningful reduction in DNA fragmentation
Greco et al J Andriol 2008
Vit.A,C,E + NAC & Zinc after variecocele surgery increase sperm
count without an impact on PR RCT Paradiso et al . World J Urol 2008
A systematic review with many limitations of 17 RCTs n= 1665
Infertile men given Vit,E,C.Zinc, selenium, folate , carnitine &
carotenoids reported that 82 % of trials showed improved sperm
quality and PR Ross et al. Reprod Biomed Online
2010
Currently no specific recommendations on the use of AOX in Rx of male
infertility and thus their use is completely empirical

20. Optimizing surgical sperm retrieval with hormonal manipulation
Concept : spermatogenesis in dependant on high intratesticular T
levels & FSH stimulation of SC
60-70% of men with NOA will have focal spermatogenesis , so the
use of CC ,AIs or Gns may be beneficial
 An increase in sperm retrieval rate at micro- TESE by 22 % was
noticed when T reached > 250ng/dl after CC, AIs, or hCG or Gns
for 3-24 months
Ramasamy et al. J Urol 2009, Reifsnuder et al. J Urol 2012

21. Conclusions
 The goal of male infertility treatment is to optimize :
LH levels to stimulate T production by Leydig cells
FSH to stimulate Sertoli Cs and spermatogenesis and
Eliminate any estrogen excess
 Hormonal therapy should not be used indiscriminately in
idiopathic male infertility due to its questionable efficacy and
restrictive cost
 Lifestyle modification : quit smoking & alcohol, wt reduction,
exercise, balanced diet ( trace elements & Antioxidants ) facilitate
spermatogenesis .

22. Medical Treatment of Female
Infertility
Factors affecting the management
Age Type &duration of infertility
Cause of infertility Prior Rx failure
 Evaluate both partners
 Provide proper information about
Act & timing of coitus
Nature of therapy
Available Rx options & their cost
 Keep in mind the probability of unexplained infertility 10-15 %
 A positive attitude of the couple is to stay motivated , not to change
consultants regularly and be compliant to Rx

23.  Lifestyle modification in PCO :
wt reduction : Increases SHBG ,
Reduces T & insulin levels
 Ovarian Causes
1- Hypo- hypo: Kalma’s, anorexia nervosa ( Low FSH,LH.E2) :
Rx with GnRH
2- PCO: Ovulation induction drugs
CC, AIs, Gns +/- ovulation facilitators : Metformin ,
pioblitazone

24. Clomiphene Citrate
CC drug of choice for women with normal TSH, PRL and endogenous
estrogen production WHO Class 2
Blocks E receptors in hypothalamus , increases GnRH production and
FSH & LH release
CC : effective in short luteal phase ( corrects FSH defect )
Start with 50mg /d d2-d6 for 3-6 cycles Check P4, Urine LH,
BBT
100 mg/d for 3-6 cycles
Consider AIs / Gn or combinations CC /Letrozple + Gns
Side effects : Thin endometrium,
Unfavourable cervical mucus.
Hot flushes ( antiestrogenic effect )
Headache, nausia, visual changes ( scotomas )
Wt gain
Risks : Multiple pregnancy & OHSS

25. CC Resistance : failure to ovulate
Add : 5mg Prednisone / 0.5 -2mg Dexamethasone in
the fol. phase
hCG shot CC + Metformin
CC+ hMG hMG 50-75 IU
Aromatase Inhibitors
Aromatase converts androgens to estrogen
Advantages : No anti-estrogenic effect on endometrium & cervix
Mono-follicular development
Letrozole is banned for use in infertility due to its teratogenicity

26. Gonadotropins
 Aim: develop single pre-ovulatory follicle
 Perform baseline vag. scan
• Start hMG 75-150 IU for 3-5 days from d3
Measure E2 : if doubles continue same dose, if not increase dose
by 50% for 3 days and repeat until E2 doubles
 Repeat scan every 2-3 days ( Fol. Measurement & ET )
 Trigger with hCG 5000-1000 IU at fol. Size 18 mm / ET at least 7
mm
 Keep in mind OHSS and multiple pregnancy

27. Hypothalamic causes : Kalma’s, anorexia nervosa
( Low FSH,LH.E2)
 RX : GnRH SC Pulsatile fasion
Less risk of OHSS vs Gns , yet
Expensive
LUF syndrome : Micronised P4 or hCG
Hyperprolactinemia : Bromocriptine 1,25mg at bed time for 7ds
Hypothroidism: L- thyroxine according to endocrinologist
evaluation

28. Laparoscopic Ovarian Drilling
PCO :
Rule of 4 : 4 puntures, 4 seconds, 4mm depth, 40 watt current
Laparoscopic Ovarian Drilling in PCO
Excessive cautery leads to adhesion formation & decreased
AMH

29. Thank
You