Combined use of phosphodiesterase-5 inhibitors and
selective serotonin reuptake inhibitors for temporary
ejaculation failure in couple undergoing assisted
Shaoming Lu, M.D., Yueran Zhao, Ph.D., Jingmei Hu, M.D., Xiao Li, M.D., Haobo Zhang, M.D.,
Li You, M.B., and Zi-jiang Chen, M.D., Ph.D.
Andrology Unit, Center For Reproductive Medicine, Provincial Hospital, Shandong University, Jinan, Shandong, People’s
Republic of China
tive technologies (ART).
Design: Case report.
Setting: Andrology unit, center for reproductive medicine.
Patient (s): Five patients suffering from temporary ejaculation failure during ART.
Intervention(s): Assistedreproductivetechnology.Semensamples werecollected bymasturbation.Thecombined
use of phosphodiesterase-5 inhibitor (PDE5-I; vardenafil, 10 mg) and selective serotonin reuptake inhibitor (SSRI;
sertraline, 50 mg) to treat patients who failed to collect semen on the day of egg retrieval.
Result(s): Five patients with unexpected ejaculation failure during ART treatments were identified; two patients
10 mg) plus SSRI (sertraline, 50 mg) enabled them to provide spermatozoa successfully. It suggested that the com-
bined protocol could be more efficient for temporary ejaculation failure than sildenafil alone. On the day of the egg
difficulty 2 h later.
Conclusion(s): The results indicate that the combined protocol of vardenafil plus sertraline could resolve the
unpredictable ejaculation failure during ART. We presume that it might be helpful for attenuating the patients’
stress and anxiety. (Fertil Steril?2009;91:1806–8. ?2009 by American Society for Reproductive Medicine.)
Key Words: Phosphodiesterase-5 inhibitor, selective serotonin reuptake inhibitor, assisted reproductive technolo-
gies, temporary ejaculation failure, anxiety
During assisted reproductive technologies (ART) treatment,
oocyteretrieval commonly follows pituitary down-regulation
band to produce fresh spermatozoa on demand for fertiliza-
tion. Unfortunately, sometimes the husband fails to collect
a semen sample on the day of egg retrieval because of psy-
chologic stress and anxiety. To our knowledge, reports about
such cases and management are scarce. The methods for
sperm recovery in this situation include taking medicine
such as phosphodiesterase-5 inhibitors (PDE5-Is; sildenafil
tatic massage (6), and invasive procedures such as rectal
probe electroejaculation (7, 8), vasal sperm aspiration (9),
percutaneous epididymal sperm aspiration (10), and testicu-
lar sperm aspiration (11, 12). These techniques, however,
are not always able to overcome the problem of sperm recov-
ery. If no sperm is available, the patients have to cancel the
treatment cycle or cryopreserve their oocytes.
We describe, for the first time, the successful combination
of PDE5-I and selective serotonin reuptake inhibitor (SSRI)
during ART treatments for unexpected ejaculation failure.
It is an efficient and noninvasive method to prevent a delay
in insemination which may compromise the ART results.
The first casewas a 29-year-old patient, 180 cm in height and
81 kg in weight. His wife was 28 years old. They were
referred for IVF because of fallopian obstruction. They de-
scribed their sexual function as regular and harmonious.
The sperm analyses were normal and the man never had dif-
the day of egg retrieval he had temporary ejaculation failure
because of stress, and we prescribed sildenafil for him. Three
hours later, the medicine had on effect and the patient asked
Received February 5, 2008; revised and accepted March 3, 2008; pub-
lished online April 28, 2008.
S.L. has nothing to disclose. Y.Z. has nothing to disclose. J.H. has nothing
to disclose. X.L. has nothing to disclose. H.Z. has nothing to disclose.
L.Y. has nothing to disclose. Z.C. has nothing to disclose.
Supported by National Basic Research Program of China, Beijing (973
Program; 2006CB944004), and National Natural Science Foundation
of China, Beijing (30670777).
Repint requests: Dr. Zi-jiang Chen, Center for Human Reproduction,
Shandong Provincial Hospital, Shandong University, 324 Jing-5-Wei-7
86-531-87068226; E-mail: firstname.lastname@example.org).
Republic of China.(FAX:
Fertility and Sterility?Vol. 91, No. 5, May 2009
Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
for help again. Taking into account the drug’s side effects and
the patient’s psychologic fragility and stress, we offered an-
other PDE5-I (vardenafil 10 mg) plus SSRI (sertraline 50
mg). One hour later, he succeeded in producing the sperm
sample containing 30 ? 106motile spermatozoa. Six of
nine oocytes were fertilized by IVF, and two embryos were
transfered 48 h later. The remaining four embryos in good
quality were frozen for future use.
The second patient was 31 years old and had been trying to
achieve pregnancy over 7 years. He never had difficulties in
providing sperm samples on demand for three IUI cycles.
lection and was prescribed 50 mg sildenafil at first. Unfortu-
nately, he still couldn’t produce the sperm sample 3 hours
later. We then prescribed vardenafil and sertraline for him.
Two hours later, we got the semen from him.
It seemed that the combined use of vardenafil and sertra-
line in such cases might attenuate the patients’ stress and
be more useful for unexpected ejaculation failure compared
with PDE5-I alone. Therefore, when the next two patients
faced the same difficulty on the day of the egg retrieval, we
directly prescribed vardenafil plus sertraline together. Both
of them collected the sperm sample two hours later without
The fifth patient was aged 36 years and his wife 35 years.
The couple had been trying to attain a pregnancy for 5 years.
This was their second IVF cycle. In their first cycle, the hus-
band had suffered from unexpected ejaculation failure and
could not produce the sperm in time. Testicular sperm aspira-
tion was performed under localanesthesia in parallel with the
oocyte retrieval. No progressively motile spermatozoa were
observed, and eight mature oocytes were retrieved and in-
jected for ICSI. Six of them degenerated after injection and
two embryos were transfered 48 h later, but no pregnancy en-
sued. The patient attributed the ejaculation failure to ‘‘anxi-
ety.’’ Because he did not have any difficulty in sperm
collection by masturbation for the second IVF treatment
nor during sexual intercourse, the couple refused sperm cryo-
preservation before IVF. However, on the day of egg collec-
tion, the husband failed again. Vardenafil and sertraline were
prescribed as with the earlier cases. The husband succeeded
tile spermatozoa. Seven embryos were attained, and three of
The diagnosis of male infertility has been associated with
a loss of self-esteem and an increase in patients’ anxiety
and somatic complaints. This situation imposes tremendous
stress on the men and may lead to unexpected ejaculation
nificant delay of the insemination procedure for IVF may
tion before insemination adversely affects the chance of fer-
tilization and developing into an embryo (1). However, it has
been demonstrated recently that some men experience sexual
dysfunction of a psychogenic nature in response to the diag-
nosis of infertility. One-third of couples undergoing infertil-
ity diagnosis and therapy said that the treatment had
a negative effect on their sexual relationship. In particular,
the male partner’s fears ofhavinglostpotencyowingtoinfer-
tility might be exacerbated by and during scheduled sexual
intercourse (14). Saleh et al. (5) reported that 405 men with
normal sexual functions who obtained the first sperm sample
without difficulty were informed that the analysis of semen
was abnormal. When the second sample was requested 2
weeks later, 46 of 405 (11%) failed to obtain sperm by mas-
turbation. All 46 men experienced problems with erection or
orgasm and had severe anxiety during attempts to masturbate
and sexual contact with their partners.
Five patients with unexpected ejaculation failure during
IVF treatments were identified in our center. All described
their sexual function as regular and harmonious and had pre-
viously been able to obtain sperm samples by masturbation
for analysis at lease twice, but they failed on the day of egg
retrieval. They attributed the unexpected failure to the strong
stress and severe anxiety.
When a patient has difficulty in producing a sperm sample
by masturbation, invasive and noninvasive methods could be
used. The invasive methods include vigorous massage of the
prostate, rectal probe electroejaculation and surgical aspira-
tion. Because anesthetic procedures and operating facilities
are required, these methods can not be applied in acute
Noninvasive methods for facilitating sperm procurement
can be proposed: help from the partner, sexual intercourse
with a nontoxic condom, the prescription of sildenafil, penile
vibration, and the viewing of a sexually stimulating video.
But they are not always effective. Saleh (5) reported that
only 20% of males undergoing infertility evaluation with
psychosexual problems were able to collect semen using
Sertraline is an SSRI used to control depression, panic dis-
order, obsessive-compulsive disorder, post-traumatic stress
disorder, social anxiety disorder, and a severe form of pre-
mature ejaculation (PE) (15–17). Chen et al. (18) identified
the efficacy of sildenafil as adjuvant therapy to SSRIs in
the treatment of PE and decreasing SSRI side effects such
as dysfunction of erection, arousal, ejaculation, and orgasm.
Theresultsshowed thatsildenafilplus SSRI hada higher suc-
application or SSRI treatment alone in terms of the Interna-
tional Index of Erectile Function scores and PE grades. The
present results showed that the combination treatment was
more effective than sildenafil alone. The first two patients
succeeded in producing sperm samples, and no side effect
was noted. This experience prompted us to offer vardenafil
Fertility and Sterility?
plus sertraline directly to patients who faced unexpected
ejaculation failure during ART treatments and all of them
succeeded in providing sperm sample easily without any
side effect. It suggested that vardenafil plus sertraline helped
the patients in producing spermatozoa on demand in an
efficacious and safe manner.
In conclusion, if no contraindications exist, vardenafil plus
sertraline for temporary erectile dysfunction during ART is
a simple and cost-effective method for men to produce sper-
compromise the ART results.
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Lu et al.
PDE5-I and SSRI for ejaculation failure
Vol. 91, No. 5, May 2009