Surgically retrieved spermatozoa versus ejaculated spermatozoa in modified natural IVF-ICSI cycles.
ABSTRACT A retrospective cohort study was performed to evaluate the outcome of modified natural IVF-intracytoplasmic sperm injection (mnIVF-ICSI) cycles to compare 81 mnIVF-ICSI first cycles using ejaculated spermatozoa with 44 mnIVF-ICSI first cycles using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved, oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated group (41.5 versus 36.5years, P=0.001). There were no significant differences in fertilization rate or cleavage rate between the ejaculated and the surgically retrieved groups; however the prevalence of embryo transfer was higher in the surgically retrieved group (65.9% versus 45.7%, P=0.03). Only single-embryo transfer was performed. Biochemical (34.5% versus 37.8%) and clinical (31.0% versus 35.1%) pregnancy rates per embryo transfer were similar between the ejaculated and the surgically retrieved groups. The data suggest that mnIVF-ICSI is an alternative treatment option in couples with severe male factor infertility where surgical sperm retrieval is required. The aim of the present study was to evaluate and compare the outcomes of modified natural IVF-intracytoplasmic sperm injection (mnIVF-ICSI) with surgically retrieved spermatozoa (in male partners with obstructive azoospermia) and ejaculated spermatozoa (in couples with mild-to-moderate male factor). Eighty-one mnIVF-ICSI first cycles using ejaculated spermatozoa were compared with forty-four mnIVF-ICSI first cycles using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved, oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated group. There were no significant differences in fertilization rate, or cleavage rate between the two groups; however, there were more patients having embryo transfers in the surgically retrieved group. Only single-embryo transfer was performed. Biochemical and clinical pregnancy rates per embryo transfer were similar between both groups. The data suggest that mnIVF-ICSI is an alternative treatment option in couples with severe male factor infertility where surgical sperm retrieval is required.
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ABSTRACT: To assess the effect of indomethacin (taken at defined times) on follicular rupture, indexes of intrafollicular blood flow, and steroidogenesis. Six healthy volunteers awaiting treatment for infertility by IVF-ET during subsequent natural cycles. All women were examined (at least every 8 hours) by transvaginal ultrasonography with color Doppler imaging and had samples of blood taken for hormone analysis. A self-test for urinary LH was performed before each scan. Indomethacin was first taken (50 mg three times per day) according to the maximum follicular diameter (first four women) or when the LH dipstick gave a positive result; the drug was taken for > or = 3 days. Follicular rupture was delayed in five of six cases (by 2 to 12 days). There was a reduction in intrafollicular peak systolic velocity before and after the positive urinary LH test compared with historical controls. Three follicles (50% of women) with the highest peak systolic velocity had an hemorrhagic appearance and persisted longer. There was no significant effect on menstrual cycle length or the levels of circulating FSH, E2, LH, or P. Indomethacin administered at the time of a positive self-test for urinary LH can delay follicular rupture with an associated reduction in intrafollicular blood flow but with no apparent effects on hormonal or menstrual status.Fertility and Sterility 04/1996; 65(3):556-60. · 4.17 Impact Factor
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ABSTRACT: To study the efficacy of a simple protocol of in vitro fertilization in the spontaneous natural cycle. A prospective study using in vitro fertilization in a natural cycle for the treatment of infertility due to tubal factor. Fifty-eight patients were monitored by vaginal ultrasound and LH in urine for 229 cycles. In 49.8% of the cycles the pick-up was canceled because of the early LH rise or failure to visualize a dominant follicle. Ovum pick-up was performed in 112 cycles and oocyte retrieval rate was 87.5%. Embryo transfer was performed in 86 cycles, pregnancy rate per pick-up was 10.2%, and there was no pregnancy wastage. IVF in a spontaneous cycle is a simple, low cost and safe treatment, which yields reasonable PR, for young regularly menstruating women with tubal factors of infertility.Journal of obstetrics and gynaecology (Tokyo, Japan) 09/1995; 21(4):337-40.
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ABSTRACT: When designing a clinical trial to show whether a new or experimental therapy is as effective as a standard therapy (but not necessarily more effective), the usual null hypothesis of equality is inappropriate and leads to logical difficulties. Since therapies cannot be shown to be literally equivalent, the appropriate null hypothesis is that the standard therapy is more effective than the experimental therapy by at least some specified amount. The problem is presented in terms of a trial in which the outcome of interest is dichotomous; test statistics, confidence intervals, and sample size calculations are discussed. The required sample size may be larger for either null hypothesis formulation than for the other, depending on the specific assumptions made. Reporting results in terms of confidence intervals is especially useful for this type of trial.Controlled Clinical Trials 01/1983; 3(4):345-53.
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Author's personal copy
Surgically retrieved spermatozoa versus
ejaculated spermatozoa in modified natural
Wael Jamala,*, Maria P Ve ´leza,b, Armand Zinia,c, Simon Phillipsa,
Robert Hemmingsa,d, Isaac-Jacques Kadocha,b
aOVO Clinic, 8000 boulevard De ´carie, Montre ´al, Que ´bec, Canada H4P 2S4;bUniversite ´ de Montre ´al, Department
of Obstetrics and Gynecology, Pavillon Roger-Gaudry, C.P. 6128, succursale Centre-Ville, Montre ´al, Que ´bec,
Canada H3C 3J7;cMcGill University, Division of Urology, Department of Surgery, St. Mary‘s Hospital, 3830 Lacombe Ave.,
Montreal, Quebec, Canada H3T 1M5;dMcGill University, Department of Obstetrics and Gynecology, St. Mary‘s Hospital,
3830 Lacombe Ave., Montreal, Quebec, Canada H3T 1M5
*Corresponding author. E-mail address: firstname.lastname@example.org (W Jamal).
Dr Wael Jamal received his BSc and MD in 1998 from the King Abdul-Aziz University in Saudi Arabia. He then
undertook his obstetrics and gynaecology residency training at McGill University, a 1-year joint fellowship
programme in minimally invasive gynaecological surgery between the University of Montreal and McGill
University Health and a 2-year reproductive endocrinology and infertility fellowship programme between the
University of Montreal and the OVO Clinic, completing in 2009. Afterwards, he joined the teaching faculty of the
University of Montreal-affiliated reproductive endocrinology and infertility fellowship programme at the OVO
Clinic. His particular research interests include the use of 3D ultrasound, sperm morphology and mild-
injection (mnIVF–ICSI) cycles to compare 81 mnIVF–ICSI first cycles using ejaculated spermatozoa with 44 mnIVF–ICSI first cycles
using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved,
oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated
group (41.5 versus 36.5 years, P = 0.001). There were no significant differences in fertilization rate or cleavage rate between the
ejaculated and the surgically retrieved groups; however the prevalence of embryo transfer was higher in the surgically retrieved
group (65.9% versus 45.7%, P = 0.03). Only single-embryo transfer was performed. Biochemical (34.5% versus 37.8%) and clinical
(31.0% versus 35.1%) pregnancy rates per embryo transfer were similar between the ejaculated and the surgically retrieved groups.
The data suggest that mnIVF–ICSI is an alternative treatment option in couples with severe male factor infertility where surgical
sperm retrieval is required.
ª 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
A retrospective cohort study was performed to evaluate the outcome of modified natural IVF–intracytoplasmic sperm
KEYWORDS: ICSI, IVF, modified natural IVF, PESA, single-embryo transfer, TESE
1472-6483/$ - see front matter ª 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Reproductive BioMedicine Online (2012) 25, 242–247
Author's personal copy
Modified natural cycle IVF (mnIVF) is a treatment modality
that was of little interest for many years but has recently
been used increasingly as an alternative option to stimu-
lated IVF cycles (Aanesen et al., 2010; Reyftmann et al.,
2007; Ubaldi et al., 2004). This change has been made pos-
sible with the introduction of gonadotrophin-releasing hor-
techniques to minimize premature ovulation in these cycles
(Kettel et al., 1991).
The benefits of mnIVF treatment are the use of minimal
amount of medication with almost no risk of ovarian hyper-
stimulation syndrome, the relatively easier oocyte retrieval
which can be done without sedation or local anaesthesia,
the lower financial burdens and the possibility to continue
with treatments on a monthly basis unlike stimulated IVF
(sIVF) where a break from treatment is required (Aanesen
et al., 2010; Pelinck et al., 2002). Furthermore, since mnIVF
almost always results in only one oocyte being aspirated,
single-embryo transfer will almost always be done, there-
fore reducing the risk of multiple birth (ESHRE, 2001;
Pandian et al., 2005).
Although the clinical pregnancy rates per cycle and per
embryo transfer in mnIVF may seem low, as reported in a lit-
erature review ranging from 0% to 18.8% and 0% to 50%,
respectively (Pelinck et al., 2002), cumulative pregnancy
rates with repeated mnIVF cycles, which are more accurate
for assessing the efficacy of mnIVF are encouraging.
Lifetime analysis from three published studies showed
cumulative pregnancy rates of 43% and 42% after three
and five oocyte aspirations (Aboulghar et al., 1995; Paulson
et al., 1992) and 46% after four started cycles (Nargund
et al., 2001). Furthermore, cancellation rates, the most
important drawback of mnIVF, have decreased after the
introduction of GnRH antagonists and indomethacin in the
late follicular phase of mnIVF without negative impact on
the clinical outcome (Paulson et al., 1994; Rongieres-Ber-
trand et al., 1999).
mnIVF has been proposed for various patient groups
including poor responders (Kadoch et al., 2011; Reyftmann
et al., 2007) and patients less than 37 years of age (Phillips
et al., 2007). Additionally, it has been offered in the study
centre as an alternative option to sIVF because of its lower
cost for eligible couples when medically indicated. More
recently, with the public funding of IVF in the province of
Que ´bec, while up to three cycles of sIVF are covered by
Medicare, up to six cycles of mnIVF, along with all its
potential advantages, can be performed (Bissonnette
et al., 2011). Indeed, some studies have reported that the
cost of mnIVF is approximately 20% lower than that of sIVF,
including average cost of cancelled cycles and the costs
related to ovarian hyperstimulation syndrome (Aboulghar
et al., 1995; Nargund et al., 2001). More recently, Polinder
et al. (2008) conducted a randomized controlled trial eval-
uating the cost-effectiveness of mild ovarian stimula-
single-embryo transfer, compared with a standard stimula-
tion/GnRH agonist long protocol and the transfer of two
embryos. The authors reported that despite a significantly
increased average number of IVF cycles using the mild strat-
egy (2.3 versus 1.7 cycles), lower average total costs were
observed over a 12-month period. This was mainly due to
higher costs of the obstetric and post-natal period for the
standard strategy, related to multiple pregnancies.
There is limited information on the use of mnIVF in male
factor infertility. The use of intracytoplasmic sperm injec-
tion (ICSI) in sIVF protocols for the treatment of male infer-
tility has benefited many couples (Palermo et al., 1992).
Both ejaculate spermatozoa and those retrieved from the
testis (testicular sperm extraction, TESE) and epididymis
(percutaneous epididymal sperm aspiration, PESA) have
been utilized in insemination of oocytes using ICSI (Craft
and Shrivastav, 1994; Temple-Smith et al., 1985). This study
centre published a case report several years ago reporting
the use of surgically retrieved spermatozoa in combination
with mnIVF and the successful birth of a healthy boy (Kadoch
et al., 2005). Following that success, the objective of the
present study was to evaluate the ongoing results of mnIVF
in combination with surgical sperm retrieval in this clinic.
Materials and methods
mnIVF and ICSI cycles in women under 37 years of age per-
formed at OVO Clinic between December 2003 and Septem-
ber 2011 were included in this retrospective cohort study.
Only first cycles that underwent oocyte retrieval were
included in the analysis. The study recruited couples with
mild-to-moderate male factor (total motile sperm count,
TMC, 1–5 million in the pre-ICSI evaluation) with an indica-
tion for IVF–ICSI. The study excluded men with severe male
factor infertility (<1 million in the pre-ICSI evaluation) or
mild male factor infertility (>5 million in the pre-ICSI eval-
uation). On the day of ICSI, only cycles with mild-to-
moderate ICSI indication (motile spermatozoa between
0.1–5 million on IVF day) were included in the study
(Figure 1). Patients were not excluded if their TMC dropped
below 1 million (but remained above 0.1 million) on the day
of ICSI as this would have resulted in a substantial drop in
the total number of cases. It was felt that couples with a
drop in their TMC (on the day of ICSI) in the range of 0.1
to 1 million would have similar outcomes to couples with
a TMC between 1 and 5 million. Couples with diagnosis of
unexplained infertility, tubal factor, low ovarian reserve,
endometriosis, sperm donor or recurrent miscarriage were
excluded from the study (Figure 1).
The mnIVF protocol has been described previously
(Kadoch et al., 2008, 2011; Phillips et al., 2007). Patients
were seen on day 9 of their cycle for an initial ultrasound.
Follicular development was monitored and GnRH antagonist
(ganirelix, Orgalutran; Merck Frosst, Kirkland, Que ´bec, Can-
ada) 0.25 mg s.c. was commenced when the dominant folli-
cle reached 14 mm; at the same time 50 mg indomethacin
(Indocid; Merck Frosst) was given three times a day until
the day before oocyte retrieval to reduce premature ovula-
tion. The use of indomethacin, a cyclooxygenase inhibitor,
has been associated with delayed follicular rupture, reduc-
ing premature ovulation (Athanasiou et al., 1996; Kadoch
et al., 2008; Morris et al., 2007; Nargund et al., 2001). Addi-
tionally, 150 IU human menopausal gonadotrophin (HMG)
Sperm source in natural-cycle IVF 243
Author's personal copy
(Repronex, Ferring Canada, North York, Ontario, Canada)
were prescribed to counteract the oestradiol drop associ-
ated with GnRH antagonist use. The three medications are
started together and administered daily (average 2.7 days)
until the day of human chorionic gonadotrophin (HCG) trig-
ger, which is administered once the follicle attains
17–18 mm (5000 IU, Pregnyl; Merck Frosst). Transvaginal
oocyte retrieval was performed 34 h later.
Semen samples wereproducedby themalepartner imme-
diately after oocyte retrieval into a sterile, sperm-tested
container. Semen was assessed at 37?C after 30 min and
prepared using density gradients of Puresperm (Nidacon,
Sweden) and washed with Gamete Buffer (Cook, Canada).
Spermatozoa from men with obstructive azoospermia
were surgically retrieved by PESA or TESE prior to the ovar-
ian stimulation cycle. PESA samples were obtained several
weeks prior to the IVF cycle, cryopreserved using Sperm
Maintenance Media (Irvine, Somagen, Canada) and subse-
quently thawed on the day of oocyte retrieval. In cases
where the PESA sample was suboptimal (e.g. rare or nonmo-
tile spermatozoa) or could not be performed prior to the
ICSI cycle, TESE was performed 24–48 h prior to oocyte
retrieval to permit culture of the tissue at 37?C (Morris
et al., 2007).
At oocyte retrieval, the oocyte was collected into Cook
Fertilization media (Cook), and prepared for ICSI by denuda-
tion of cumulus cells using cumulase (Origio, New Jersey
USA). Assessment of maturity for ICSI at metaphase II was
assessed by noting extrusion of the first polar body. In addi-
tion, birefringence technology was used to assess spindle
presence and location using a polscope (Oosight; CRi, USA).
Fertilization was confirmed by assessment of two pronuclei
18 h post-sperm injection and embryo transfer was per-
formed on day 2.
Biochemical pregnancy was assessed by serum bHCG con-
centration 15 days post-embryo transfer (bHCG higher than
25 IU) and confirmed by ultrasound evidence of an intrauter-
ine fetal heart at 8 weeks (clinical pregnancy). Live birth
rates were calculated for those patients with estimated
date of delivery before October 2011.
Statistical analysis was based on the assumption that
clinical pregnancy rates per embryo transfer in mnIVF–ICSI
cycles are approximately 30% and that the difference
between both groups of sperm source will be less than 25%,
Flow chart of study participants.
244 W Jamal et al.
Author's personal copy
a minimum of 41 cycles per group will have a power of 0.80
(alpha 0.05) to test the noninferiority of surgically retrieved
(Blackwelder, 1982). Statistical analysis was performed
using STATA 10.0 (StataCorp, Texas, USA). Proportion com-
parisons were performed by chi-square or Fisher Exact
test. The Student t-test was used to compare means. A
P-value <0.05 was considered to be statistically significant.
The study was undertaken as a clinical quality control
evaluation and was properly reviewed and approved by
the scientific review committee (granted 15 February 12).
A total of 726 first mnIVF cycles were performed in the study
centre between December 2003 and September 2011.
Ninety-two (12%) were cancelled before oocyte retrieval.
In the 634 cycles that underwent oocyte retrieval, at least
one oocyte was recovered in 553 cycles: an oocyte recovery
rate of 87.2% (Figure 1).
After excluding the noneligible couples, (Figure 1) 81
first mnIVF–ICSI cycles utilizing ejaculated spermatozoa
were compared with 44 cycles using surgically retrieved
spermatozoa (PESA, 30 cycles; TESE, 14 cycles). The ejacu-
lated sperm group comprised patients with mild-to-
moderate ICSI indication (mobile spermatozoa between
0.1–5 million on IVF day; mean ± SD 1.41 million ± 1.40 mil-
lion). All the patients in the surgically retrieved sperm group
had a diagnosis of obstructive azoospermia (prior vasec-
tomy, vasectomy reversal failure or congenital bilateral
absent vas deferens), except one with presumed obstructive
azoospermia (with a normal exam and serum FSH, and a nor-
mal karyotype and no Y chromosome microdeletion).
The descriptive characteristics of the two groups can be
seen in Table 1. There were no differences between the two
groups in terms of the female age, number of oocytes col-
lected or oocyte maturity. The male age in the surgically
retrieved sperm group was significantly higher than in the
ejaculated sperm group (41.5 versus 36.5 years, P = 0.001).
Cycle and obstetric outcomes are shown in Table 2.
There were no differences in terms of fertilization rate or
cleavage rate between the two groups. Assisted hatching
was performed equally in both groups. A higher rate of
embryo transfer was found in the surgically retrieved sperm
group (65.9% versus 45.7%; P = 0.03). Single-embryo transfer
was performed in all cases. There were no significant
differences between the biochemical pregnancy rate per
oocyte retrieval or per embryo transfer. Similarly, there
were no significant differences between the clinical preg-
nancy rate per oocyte retrieval or per embryo transfer. Only
singleton pregnancies were identified on the day of the via-
Twelve out of 22 patients having a positive clinical preg-
nancy had an estimated date of delivery before 31 October
2011. In this group, live birth rates per embryo transfer
were similar between surgically and ejaculated spermato-
zoa respectively (5/31, 16.1% versus 7/27, 25.9%, P = 0.4).
As far as is known, this is the largest retrospective cohort
study of couples with male factor infertility comparing the
clinical outcomes of mnIVF with ejaculated versus surgically
retrieved spermatozoa. The study found no differences in
terms of fertilization rate or cleavage rate between the
ejaculated and surgically retrieved sperm groups. However,
higher rates of embryo transfer were found in the surgically
retrieved sperm group. Single-embryo transfer was per-
formed in all cases. There were no differences in the bio-
chemical or the clinical pregnancy rate. Of note, all
ongoing clinical pregnancies at the 8-week ultrasound were
A few authors have evaluated the outcomes of mnIVF and
ICSI using ejaculated spermatozoa in cases of male factor
infertility. Ubaldi et al. (2004) assessed 157 couples with
severe male factor infertility and poor ovarian response
who underwent a total of 258 natural ICSI cycles. Thirty-two
cycles were cancelled before oocyte retrieval. In the 226
cycles that underwent oocyte retrieval, at least one oocyte
was recovered in 193 cycles with an oocyte recovery rate of
85.4%. The authors were able to perform an embryo transfer
in only 51.5% (133/258) of the started cycles. In the current
study, however, the proportion of embryo transfer was
lower in the ejaculated group (45.7%) and higher in the sur-
gically retrieved sperm group (65.9%), respectively. Ubaldi
et al. (2004) reported clinical pregnancy rates of 22.2%
per patient and 26.3% per embryo transfer. The current
study obtained similar results, with clinical pregnancy rates
surgically retrieved spermatozoa.
Demographic comparison between ejaculated spermatozoa and
Female age (years)
Male age (years)
No. of oocytes collected
31.7 ± 3.2
36.5 ± 6.2
1.06 ± 0.29
32.0 ± 3.2
41.5 ± 8.3
1.02 ± 0.15
Data are mean ± SD or % (n/total oocytes).
NS = not statistically significant.
at-test equal variances.bt-test unequal variances.
cFisher Exact test.
Sperm source in natural-cycle IVF 245
Author's personal copy
of 16.0% and 20.5% per oocyte retrieval and 35.1% and 31.0%
per embryo transfer in the ejaculated and the surgically
retrieved groups, respectively. These results are comparable
to studies of poor responders (Bassil et al., 1999) and nor-
mally responding younger women (Janssens et al., 2000;
Ng et al., 2001).
Recently, Jones and Liu (2011) published a case report of
a 35-year-old woman with significantly elevated FSH con-
centrations, regular menses and severe male factor infertil-
ity who conceived after her third mnIVF attempt with ICSI,
recommending mnIVF as an option prior to considering
oocyte donation when a secondary cause of infertility
necessitates ICSI. In this study centre’s previously published
case report, a 35-year-old woman and her 43-year-old
spouse diagnosed with secondary infertility were referred
for assisted reproduction due to decreased ovarian reserve
and male factor infertility with unsuccessful vasectomy
reversal (Kadoch et al., 2005). Following the previously
described mnIVF protocol, oocyte retrieval was performed
good-quality embryo was accomplished in this first cycle;
however, no pregnancy was achieved. Subsequently, a sec-
ond mnIVF cycle was performed with successful oocyte
retrieval and fertilization using a sample of the remaining
frozen spermatozoa obtained with PESA. As result of this
second mnIVF cycle, a healthy baby boy was delivered at
37 weeks’ gestation. Supported by this initial case report,
it was suggested considering mnIVF as an alternative option
for infertile women who have normal ovulatory menstrual
cycles; and when necessary, ICSI could be performed using
spermatozoa retrieved by PESA (Kadoch et al., 2005).
In most studies to date, the source of spermatozoa (ejac-
ulated, epididymal or testicular) used in ICSI cycles has had
within the context of single-embryo transfer (Nagy et al.,
1995; Nilsson et al., 2007). Moreover, there is no difference
in reproductive outcomes whether fresh or frozen spermato-
zoa are used in ICSI (Nagy et al., 1995). Nonetheless, the
arenodata toshow evena modestimpactof spermsourceon
ICSI outcomes, if there were such an effect it would poten-
tially be best demonstrated in the context of a single oocyte
injection (as in a mnIVF). Therefore, this study assumed that
didymal or testicular) would adversely impact reproductive
outcomes when compared with the use of a single ejaculated
spermatozoa. The fact that this study observed no effect of
sperm source on mnIVF outcomes further supports the pre-
mise that the source of spermatozoa has no significant
impact on ICSI reproductive outcomes in general.
The primary limitation of this study is its relatively small
sample size. This limited its ability to adjust for a broad
range of potential covariates, including female factors,
although the selection of women younger than 37 years
would decrease confounding by female age. Although the
sample size is large enough to indicate that the use of sur-
gically retrieved spermatozoa does not have an important
and significant adverse impact on reproductive outcomes
following mnIVF (i.e. >25% reduction in clinical pregnancy
rates), we cannot exclude the possibility that the use of sur-
gically retrieved spermatozoa could have a more modest
adverse effect on clinical outcomes.
Additionally, while only first mnIVF cycles were included
in this study, some couples had previously undergone stim-
ulated cycles at the study clinic or in another institution.
In fact, while most of the patients (78.5%) did not have a
prior stimulated cycle, 15.6% had one and 5.9% had between
three and six previous stimulated cycles (data not shown).
Nonetheless, since the distribution was similar in both
groups, if this would introduce a bias, it would not have
an impact on the interpretation of the results.
These results allow the conclusion that, for couples with
obstructive azoospermia, mnIVF could be a reasonable
alternative to conventional sIVF where occasionally one
may have a larger number of oocytes than spermatozoa
surgically retrieved spermatozoa.
Comparison of outcome measures between ejaculated spermatozoa and
Cycles with embryo transfera
Cycles with assisted hatching
Per oocyte retrieval
Per embryo transfer
Per oocyte retrieval
Per embryo transfer
Data are n (% per cycle) or n/total (%).
aSignificantly higher for surgical retrieval (P = 0.03, t-test).
246 W Jamal et al.
Author's personal copy
for the IVF cycle. mnIVF may be considered in couples
where the man has had a vasectomy, if the partner is
eligible for mnIVF. The data demonstrates that the need
to surgically retrieve spermatozoa should not be a contrain-
dication to using mnIVF.
The authors would like to thank the clinical and laboratory
teams at OVO Clinic for all their work on these cycles.
MPV is supported by a CIHR fellowship award.
Aanesen, A., Nygren, K.G., Nylund, L., 2010. Modified natural cycle
IVF and mild IVF: a 10 year Swedish experience. Reprod. Biomed.
Online 20, 156–162.
Aboulghar, M.A., Mansour, R.T., Serour, G.A., Amin, Y.M., Sattar,
M.A., Ramzy, A.M., 1995. In vitro fertilization in a spontaneous
cycle: a successful simple protocol (Tokyo 1995). J. Obstet.
Gynaecol. 21, 337–340.
Athanasiou, S., Bourne, T.H., Khalid, A., Okokon, E.V., Crayford,
T.J., Hagstrom, H.G., Campbell, S., Collins, W.P., 1996. Effects
of indomethacin on follicular structure, vascularity, and func-
tion over the periovulatory period in women. Fertil. Steril. 65,
Bassil, S., Godin, P.A., Donnez, J., 1999. Outcome of in-vitro
fertilization through natural cycles in poor responders. Hum.
Reprod. 14, 1262–1265.
Bissonnette, F., Phillips, S.J., Gunby, J., Holzer, H., Mahutte, N.,
St-Michel, P., Kadoch, I.J., 2011. Working to eliminate multiple
pregnancies: a success story in Quebec. Reprod. Biomed. Online
Blackwelder, W.C., 1982. ‘Proving the null hypothesis’ in clinical
trials. Control Clin. Trials 3, 345–353.
Craft, I., Shrivastav, P., 1994. Treatment of male infertility. Lancet
ESHRE, 2001. Prevention of twin pregnancies after IVF/ICSI by single
embryo transfer. ESHRE Campus Course Report. Hum. Reprod.
Janssens, R.M., Lambalk, C.B., Vermeiden, J.P., Schats, R.,
Schoemaker, J., 2000. In-vitro fertilization in a spontaneous
cycle: easy, cheap and realistic. Hum. Reprod. 15, 314–318.
Jones, C., Liu, K., 2011. Pregnancy after modified natural cycle IVF:
case report of a young patient with elevated FSH levels and male
factor infertility. J. Obstet. Gynaecol. Can. 33, 139–141.
Kadoch, I.J., Phillips, S.J., Hemmings, R., Lapensee, L., Couturier,
B., Bissonnette, F., 2005. Ongoing pregnancy after ICSI of
frozen-thawed PESA-retrieved spermatozoa and IVF in a con-
trolled natural cycle. Reprod. Biomed. Online 10, 650–652.
Kadoch, I.J., Al-Khaduri, M., Phillips, S.J., Lapensee, L., Couturier,
B., Hemmings, R., Bissonnette, F., 2008. Spontaneous ovulation
rate before oocyte retrieval in modified natural cycle IVF with
Kadoch, I.J., Phillips, S.J., Bissonnette, F., 2011. Modified natu-
ral-cycle in vitro fertilization should be considered as the first
approach inyoungpoor responders.
Kettel, L.M., Roseff, S.J., Chiu, T.C., Bangah, M.L., Vale, W.,
Rivier, J., Burger, H.G., Yen, S.S., 1991. Follicular arrest during
the midfollicular phase of the menstrual cycle: a gonadotro-
pin-releasing hormone antagonist imposed follicular-follicular
transition. J. Clin. Endocrinol. Metab. 73, 644–649.
Morris, D.S., Dunn, R.L., Schuster, T.G., Ohl, D.A., Smith, G.D.,
2007. Ideal culture time for improvement in sperm motility from
testicular sperm aspirates of men with azoospermia. J. Urol.
178, 2087–2091, discussion 2091.
Nagy, Z., Liu, J., Cecile, J., Silber, S., Devroey, P., van Steirteg-
hem, A., 1995. Using ejaculated, fresh, and frozen-thawed
epididymal and testicular spermatozoa gives rise to comparable
results after intracytoplasmic sperm injection. Fertil. Steril. 63,
Nargund, G., Waterstone, J., Bland, J., Philips, Z., Parsons, J.,
Campbell, S., 2001. Cumulative conception and live birth rates
in natural (unstimulated) IVF cycles. Hum. Reprod. 16, 259–262.
Ng, E.H., Chui, D.K., Tang, O.S., Lau, E.Y., Yeung, W.S., Chung,
H.P., 2001. In vitro fertilization and embryo transfer during
natural cycles. J. Reprod. Med. 46, 95–99.
Nilsson, S., Waldenstrom, U., Engstrom, A.B., Hellberg, D., 2007.
Single blastocyst transfer after ICSI from ejaculate spermatozoa,
percutaneous epididymal sperm aspiration (PESA) or testicular
sperm extraction (TESE). J. Assist. Reprod. Genet. 24, 167–171.
Palermo, G., Joris, H., Devroey, P., van Steirteghem, A.C., 1992.
Pregnancies after intracytoplasmic injection of single sperma-
tozoon into an oocyte. Lancet 340, 17–18.
Pandian, Z., Templeton, A., Serour, G., Bhattacharya, S., 2005.
Number of embryos for transfer after IVF and ICSI: a Cochrane
review. Hum. Reprod. 20, 2681–2687.
Paulson, R.J., Sauer, M.V., Francis, M.M., Macaso, T.M., Lobo, R.A.,
1992. In vitro fertilization in unstimulated cycles: the University
of Southern California experience. Fertil. Steril. 57, 290–293.
Paulson, R.J., Sauer, M.V., Lobo, R.A., 1994. Addition of a
gonadotropin releasing hormone (GnRH) antagonist and exoge-
nous gonadotropins to unstimulated in vitro fertilization (IVF)
cycles: physiologic observations and preliminary experience. J.
Assist. Reprod. Genet. 11, 28–32.
Pelinck, M.J., Hoek, A., Simons, A.H., Heineman, M.J., 2002.
Efficacy of natural cycle IVF: a review of the literature. Hum.
Reprod. Update 8, 129–139.
Phillips, S.J., Kadoch, I.J., Lapensee, L., Couturier, B., Hemmings,
R., Bissonnette, F., 2007. Controlled natural cycle IVF: experi-
ence in a world of stimulation. Reprod. Biomed. Online 14,
Polinder, S., Heijnen, E.M., Macklon, N.S., Habbema, J.D., Fauser,
B.J., Eijkemans, M.J., 2008. Cost-effectiveness of a mild
compared with a standard strategy for IVF: a randomized
comparison using cumulative term live birth as the primary
endpoint. Hum. Reprod. 23, 316–323.
Reyftmann, L., Dechaud, H., Loup, V., Anahory, T., Brunet-Joyeux,
C., Lacroix, N., Hamamah, S., Hedon, B., 2007. Natural cycle
in vitro fertilization cycle in poor responders. Gynecol. Obstet.
Fertil. 35, 352–358.
Rongieres-Bertrand, C., Olivennes, F., Righini, C., Fanchin, R.,
Taieb, J., Hamamah, S., Bouchard, P., Frydman, R., 1999.
Revival of the natural cycles in in-vitro fertilization with the use
of a new gonadotrophin-releasing hormone antagonist (Cetror-
elix): a pilot study with minimal stimulation. Hum. Reprod. 14,
Temple-Smith, P.D., Southwick, G.J., Yates, C.A., Trounson, A.O.,
de Kretser, D.M., 1985. Human pregnancy by in vitro fertilization
(IVF) using sperm aspirated from the epididymis. J. In Vitro Fert.
Embryo Transf. 2, 119–122.
Ubaldi, F., Rienzi, L., Ferrero, S., Baroni, E., Iacobelli, M.,
Sapienza, F., Minasi, M.G., Cobellis, L., Romano, S., Scarselli,
F., Greco, E., 2004. Natural in vitro fertilization cycles. Ann. NY
Acad. Sci. 1034, 245–251.
Declaration: The authors report no financial or commercial
conflicts of interest.
Received 4 February 2012; refereed 6 June 2012; accepted 12 June
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