TABLE 1.

University Based ART Laboratory Private ART Laboratory

25th percentile Median 75th percentile 25th percentile Median 75th percentile p-value

Volume (mL)(n¼19) 1.7 3.3 4.1 1.75 3.2 4.5 0.43

Motility (%)(n¼19) 40 40 50 16.9 56 69.2 0.07
Concentration (million/mL)(n¼20) 0.45 10 44 0.89 7 26 0.30
Total Motile Sperm (N/ejaculate)(n¼19) 0.3 8 54 0.35 9 31 0.44
Morphology (%)(n¼9) 6.5 7 10 2 3 6 0.01

O-29 Monday, October 19, 2015 12:15 PM
CLOMID HAS GOT A BRIGHT SIDE AND A DARK SIDE. WHAT DO
WE REALLY KNOWAFTER ALL THESE YEARS? EVIDENCE FOR
TOXICITY. R. Wiehle G. K. Fontenot. Research and Development,
Repros Therapeutics Inc, The Woodlands, TX.
OBJECTIVE: Clomid has been approved in women with PCOS/ovulation
induction. In men it is used off-label to increase testosterone or to relieve
symptoms of androgen abuse. Clomid is a mixture of two isomers: zuclomi-
phene and enclomiphene. The former is a weak estrogen agonist and the latter
is a strong estrogen antagonist. Repros Therapeutics is developing enclomi-
phene for elevating endogenous testosterone in men with secondary hypogo-
nadism.
DESIGN: We have administered each isomer of clomid to mice, both
chronically and acutely, in an attempt to determine the relative differences.
MATERIALS AND METHODS: Enclomiphene and zuclomiphene were
separated from clomiphene as pure mono-isomers. Mice were administered
each isomer chronically (90 days) then tissues were examined histologic.
In a mouse ADME, pigmented mice were acutely administered each of the
14C-labelled isomers. Tissue and fluid distribution were followed up to 45
days.
RESULTS: In animals chronically administered each isomer, zuclomi-
phene had pernicious effects on the male reproductive tract (testes, epidid-
ymis, and seminal vesicles) and the kidney. Significant reduction in size of
testes with testicular degeneration was seen, including Leydig cell loss
with absence of sperm in the seminiferous tubules and reduction in size of
the epididymis, seminal vesicles and kidneys. In the ADME study, for 47 tis-
sues assessed, 97.5% of the 14C-enclomiphene seen at 4 hours was lost by 24
hours. In contrast, only 40.8% of the 14C-zuclomiphene seen at 4 hours was
lost. Zuclomiphene was retained selectively. Among those that accumulated
zuclomiphene that seen in the blood were the pigmented portions of the eye,
the brain, adrenal gland, the kidneys and the testes.
CONCLUSIONS: We infer that zuclomiphene accumulates in excess over
enclomiphene. Human studies have suggested this as well. We concede that
the antagonist effects of enclomiphene can overwhelm effects of zuclomi-
phene when used chronically, however the extreme high build-up of the
agonist isomer may have lasting effects. These results justify the case for a
monoisomeric preparation and the development of Enclomiphene citrate,
for clinical use in men with secondary hypogonadism to increase testos-
terone. It is interesting to speculate whether clomiphene citrate would have
been granted FDA approval given the differences between its constitutive
isomers.
Supported by: Repros Therapeutics Inc.
O-30 Monday, October 19, 2015 12:30 PM
THE EFFECT OF CLOMIPHENE CITRATE IN THE TREATMENT
OF SUBFERTILE MALES WITH BODY MASS INDEX (BMI) ‡ 25
KG/M2. B. Patel,a T. Shah,a D. Shin.b aUrology, Rutgers New Jersey
Medical School, Newark, NJ; bUrology, Hackensack University Medical
Center, Hackensack, NJ.
OBJECTIVE: Elevated BMI has been shown to have a negative impact on
male fertility. Clomiphene citrate (CC), a selective estrogen receptor modu-
lator, is often used in the empiric treatment of subfertile males to increase
testosterone levels and improve spermatogenesis. The objective of this study
was to assess the effect of CC in the treatment of subfertile males with
elevated BMI R 25 kg/m2.
DESIGN: Retrospective cohort study.
MATERIALS AND METHODS: Fifty-six subfertile males with BMI
R 25 kg/m2 were treated with CC between 2009 and 2014. Semen analysis
was conducted on all 56 patients at baseline and at minimum, 3 months
follow-up. Fifty of the 56 patients had baseline and 5 month follow-up mea-
surements of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
total testosterone (TT), bioavailable testosterone (BT) and estradiol (E)
levels. Pregnancy status was obtained when possible. Paired t-test was
used to compare baseline and follow-up hormonal profiles and semen ana-
lyses.
RESULTS: Significant increase in sperm concentration, from 19.0
2.7
M to 28.2
4.0 M (p<0.05) was observed in men treated with CC. Subgroup
of 50 patients showed significant changes in FSH, LH, TT, BT, and E levels
(p<0.05) after five months of CC therapy.
Fifteen of 56 subjects (26.8%) achieved pregnancy, including 4/28
(14.3%) conceiving through natural intercourse, 5/16 (31.3%) through intra-
uterine insemination and 6/12 (50%) through in-vitro fertilization. Three pa-
tients reported weight gain, two had elevated liver function tests and one
complained of minor headaches.
CONCLUSIONS: Subfertile males with BMI R 25 kg/m2 who were
treated with CC therapy showed significant improvement in their hormonal
profile and sperm concentration. CC therapy was well tolerated with minimal
adverse side effects. Use of assistive reproductive techniques along with CC
empiric medical therapy may be associated with successful conception for
infertile couples.
Baseline vs. Post-Clomiphene Citrate Therapy
Parameter Baseline 5 Months P-value
FSH (mIU/mL) 4.9
0.4 6.8
0.6 <0.05
LH (mIU/mL) 4.2
0.2 6.1
0.4 <0.01
TT (ng/dL) 320.4
17.4 543.4
24.6 <0.01
BT (ng/dL) 164.3
8.8 304.4
21.0 <0.01
E (pg/mL) 23.7
1.4 36.0
2.7 <0.01
Sperm Concentration (M/mL) 19.0
2.7 28.8
4.0 <0.05
Total Motile Count (M) 30.0
6.1 50.4
11.9 0.13
PREIMPLANTATION GENETIC DIAGNOSIS
O-31 Monday, October 19, 2015 11:15 AM
A PROSPECTIVE, BLINDED, NON-SELECTION STUDY TO
DETERMINE THE PREDICTIVE VALUE OF PLOIDY RESULTS
USING A NOVEL METHOD OF TARGETED AMPLIFICATION
BASED NEXT GENERATION SEQUENCING (NGS) FOR COMPRE-
HENSIVE CHROMOSOME SCREENING (CCS). M. D. Werner,
J. M. Franasiak, K. H. Hong, C. R. Juneau, X. Tao, J. Landis,
K. M. Upham, N. R. Treff, R. T. Scott. RMA, NJ, NJ.
OBJECTIVE: NGS technologies are now being utilized for CCS with
promises to increase throughput and decrease costs. Unfortunately, these
technologies have not been validated clinically. Most concerning is the
lack of data documenting the false abnormal rate, defined as the proportion
of embryos labeled as aneuploid through NGS but which would have
delivered a healthy infant had they not been discarded. This study utilizes
a non-selection design where embryos are transferred without knowledge
of the NGS CCS result to determine the predictive value of both aneuploid
and euploid results.
DESIGN: Prospective, blinded, non-selection study.

e12 ASRM Abstracts Vol. 104, No. 3, Supplement, September 2015