prescribed medications and sperm production and function during ivf

2
was limited to only patients undergoing a day three embryo transfer. A clinical pregnancy was defined as the identification of a positive fetal heart beat. Statistical analysis included chi-square analysis for categorical data and un-paired Student’s t-test for continuous variables. A p-value less than 0.05 was considered significant. Results: 1353 patients were included in the study. 2.8% (/ 7.3) of all mature oocytes were triploid. The overall clinical pregnancy rate was 49.4%. Thirty-four (2.5%) of the patients had significant triploidy (defined as greater than 25% of all mature, injected oocytes). See the table for the comparison between patients with and without significant digynic triploidy. Patients with significant triploidy were less likely to achieve a clinical pregnancy. Patients with significant triploidy were also more likely not to undergo an embryo transfer. Impact of Significant Digynic Triploidy after ICSI Significant Triploidy No Significant Triploidy P value Number 34 1319 Normal fert (2PN/mature) 42% 73% 0.001 No transfer 20.6% 5.6% 0.003 Pregnant 35.3% 61.84% 0.0017 Clinical pregnancy 29.4% 49.9% 0.018 Implantation rate 18.5% 27.7% 0.13 Pregnancy data is per retrieval. Conclusions: The presence of significant digynic triploidy after ICSI is a very poor prognostic sign. These patients are more likely to be cancelled and, if transferred, are less likely to achieve a clinical pregnancy. Because the presence of digynic triploidy after ICSI is mostly related to oocyte factors, this finding neccesitates careful consideration from the clinician in a subsequent attempt. Supported by: None. P-352 Comparing the effects of GnRH-a on endometrial receptivity in pa- tients undergoing ART and prepared frozen embryo transfer cycles. Omur Taskin, Gokhan Akkoyunlu, Mehmet Simsek, Ramazan Demir, Ah- met Onoglu, Salih Sadik. Akdeniz Univ, Antalya, Turkey; SSK Tepecik, Izmir, Turkey. Objective: To compare the effects of short S.C and long-term depot GnRH-a on endometrial receptivity in patients undergoing ART and pre- pared frozen embryo transfer cycles. Design: Prospective randomized clinical study. Materials/Methods: Infertile women who were prepared for prepared frozen embryo transfer were consented to receive either one injection of depot tryptorelin 3.6 mg /hormone replacement (Gr. A;n:6) or 3 monthly injection of 3.6 mg tryptorelin followed by hormone replacement (Gr.B;n:5) to prepare the endometrium. Another group of patients (n:4) whose ovum pickups were cancelled due to negative TESE and used S.C. GnRH-a beginning on day 25 of previous cycle were included in the trial. Endome- trial biopsies were obtained 3 days after the progesterone replacement and 5 days after the HCG injection for the ART patients. Immunohistochemical staining intensity and distribution(HSCORE) of alphav/beta3 subunits inte- grins and traditional histologic endometrial dating were compared. Results: There were no differences among groups with respect to baseline characteristics. The changes in endometrial receptivity as determined by integrin positivity and HSCORE were similar between the groups. All the samples were in phase histologically. Integrin alphav/beta3 expression and intensity of staining as measured by the mean HSCORE was similar between the long-term use of depot GnRH-a Gr A, Gr B and short-term S.C. GnRH-a groups. However, the HSCORE measurements were lower in the S.C. GnRH-a group whereas prepared cycles HSCORE and the integrin expression were more consistent than the S.C group underwent ART. Conclusions: In the present study, endometrial receptivity was similarly enhanced both in long-term depot form groups. Prepared frozen cycle patients formed a uniform model since only the length of GnRH-a use was manipulated between the groups thus providing objective samples to eval- uate the pure GNRH-a effects. However, ART group with short S.C. GnRH-a use showed decreased integrin staining intensity (HSCORE p:0.62) which may be attributable to the effects of follicular stimulation and altered hormonal status on the endometrial maturation. Thus we may conclude that ovarian stimulation is the major factor altering the endometrial receptivity in ART than the use of GNRH-a. Supported by: none. P-353 Establishment of in vitro maturation system (IVM-IVF) as a routine ART procedure by combination of HCG administration and frozen- thawed embryo transfer. Aisaku “Isaac” Fukuda, Yoshiharu Nakaoka, Masatake Tohnaka, Hidetaka Okada, Hirotsugu Oku, Yoshiharu Morimoto. IVF Osaka Clin, Higashi-Osaka City, Japan. Objective: In vitro fertilization of in vitro matured oocytes (IVM-IVF) is hardly used as a routine ART procedure due to low pregnancy outcome. IVM-IVF is a relatively new method of ART and its methodology should be improved. However, it has numerous benefits such as less stressful physi- cally, mentally and economically, less time consuming and no risks of gonadotropins administrated. The present study was conducted to establish IVM-IVF as a standard ART procedure by selecting either fresh or frozen- thawed embryo transfer depending on endometrium thickness at oocyte retrieval and by administrating HCG on previous number of immature oocytes retrieved. Design: IVM-IVF was applied on the patients with PCOS or having at least unilateral ovary appearing PCO like echo image. Repeated IVF failure cases that desired to have this treatment were another indication. Pregnancy outcomes from Oct 1999 to Dec 2001 were analyzed. Materials/Methods: Immature oocytes were retrieved when patients had at least two small follicles more than 8 mm in diameter and before devel- opment of a dominant follicle more than 14 mm. When endometrial thick- ness was 8 mm or more at oocyte retrieval, embryos were transferred in fresh cycles. In case of endometrial thickness less than 8 mm, two-pro- nuclear oocytes or cleaved embryos were frozen for future frozen-thawed transfer in hormone-supplemented cycles. Ten thousand unit of HCG was administered 36 hours before retrievals for the patients who did not get more than 2 eggs. Immature oocytes were cultured for 24 hrs and ICSI was performed on matured oocytes. Day three embryos were transferred after biochemical assisted hatching either in fresh or in frozen-thawed cycles. Pregnancy outcomes and other parameters were analyzed. Results: Maturation rate was 43% (870/2018) in 24 hours and 80% (695/870) of matured eggs were fertilized by ICSI. A total of 26 pregnancies (15% per 178 transfers and 17% per 149 patients) were achieved in either fresh (17) or frozen-thawed transfer (9). Miscarriage rate was 31% (8/26) overall. As of Jan 2002, 14 normal babies (1 set of twin) were born from 13 deliveries. The PCOS patient ratio in pregnant cases from fresh transfer (82%) was significantly higher compared to frozen-thawed transfer cycles (33%). Two pregnancies in fresh transfer were achieved after HCG admin- istration. Conclusions: IVM-IVF is enrolled into our routine ART program. The pregnancy rate of IVM-IVF is lower compare to stimulation cycles, but this rate is acceptable when numerous benefits of unstimulated cycles were taken into account. The present study suggests that IVM-IVF can be one of the routine ART procedures and will be potentially an alternative for stimulation IVF cycles. The development of IVM culture media needs to be strongly pursued. Supported by: None. P-354 Prescribed medications and sperm production and function during IVF. Lucy Lu, Xavier Sanchez, Cory Look, Joy Lacsamana, Erlinda Macanas, Lewis Krey. Program for IVF, Reproductive Surg & Infertility, New York Univ Medical Ctr, New York, NY. Objective: Men participating in an IVF cycle often take prescribed medications whose impact on ART outcome is unreported. Although the influences of several medications upon semen parameters have been studied previously, their impact on sperm fertilization ability and resultant embryo development remain unknown. This study evaluates the effects of several groups of commonly prescribed medications on sperm production and function. S232 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002

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Page 1: Prescribed medications and sperm production and function during IVF

was limited to only patients undergoing a day three embryo transfer. Aclinical pregnancy was defined as the identification of a positive fetal heartbeat. Statistical analysis included chi-square analysis for categorical dataand un-paired Student’s t-test for continuous variables. A p-value less than0.05 was considered significant.

Results: 1353 patients were included in the study. 2.8% (�/� 7.3) of allmature oocytes were triploid. The overall clinical pregnancy rate was49.4%. Thirty-four (2.5%) of the patients had significant triploidy (definedas greater than 25% of all mature, injected oocytes). See the table for thecomparison between patients with and without significant digynic triploidy.Patients with significant triploidy were less likely to achieve a clinicalpregnancy. Patients with significant triploidy were also more likely not toundergo an embryo transfer.

Impact of Significant Digynic Triploidy after ICSI

SignificantTriploidy

No SignificantTriploidy P value

Number 34 1319Normal fert (2PN/mature) 42% 73% �0.001No transfer 20.6% 5.6% 0.003Pregnant 35.3% 61.84% 0.0017Clinical pregnancy 29.4% 49.9% 0.018Implantation rate 18.5% 27.7% 0.13

Pregnancy data is per retrieval.

Conclusions: The presence of significant digynic triploidy after ICSI is avery poor prognostic sign. These patients are more likely to be cancelledand, if transferred, are less likely to achieve a clinical pregnancy. Becausethe presence of digynic triploidy after ICSI is mostly related to oocytefactors, this finding neccesitates careful consideration from the clinician ina subsequent attempt.

Supported by: None.

P-352

Comparing the effects of GnRH-a on endometrial receptivity in pa-tients undergoing ART and prepared frozen embryo transfer cycles.Omur Taskin, Gokhan Akkoyunlu, Mehmet Simsek, Ramazan Demir, Ah-met Onoglu, Salih Sadik. Akdeniz Univ, Antalya, Turkey; SSK Tepecik,Izmir, Turkey.

Objective: To compare the effects of short S.C and long-term depotGnRH-a on endometrial receptivity in patients undergoing ART and pre-pared frozen embryo transfer cycles.

Design: Prospective randomized clinical study.Materials/Methods: Infertile women who were prepared for prepared

frozen embryo transfer were consented to receive either one injection ofdepot tryptorelin 3.6 mg /hormone replacement (Gr. A;n:6) or 3 monthlyinjection of 3.6 mg tryptorelin followed by hormone replacement (Gr.B;n:5)to prepare the endometrium. Another group of patients (n:4) whose ovumpickups were cancelled due to negative TESE and used S.C. GnRH-abeginning on day 25 of previous cycle were included in the trial. Endome-trial biopsies were obtained 3 days after the progesterone replacement and5 days after the HCG injection for the ART patients. Immunohistochemicalstaining intensity and distribution(HSCORE) of alphav/beta3 subunits inte-grins and traditional histologic endometrial dating were compared.

Results: There were no differences among groups with respect to baselinecharacteristics. The changes in endometrial receptivity as determined byintegrin positivity and HSCORE were similar between the groups. All thesamples were in phase histologically. Integrin alphav/beta3 expression andintensity of staining as measured by the mean HSCORE was similarbetween the long-term use of depot GnRH-a Gr A, Gr B and short-term S.C.GnRH-a groups. However, the HSCORE measurements were lower in theS.C. GnRH-a group whereas prepared cycles HSCORE and the integrinexpression were more consistent than the S.C group underwent ART.

Conclusions: In the present study, endometrial receptivity was similarlyenhanced both in long-term depot form groups. Prepared frozen cyclepatients formed a uniform model since only the length of GnRH-a use wasmanipulated between the groups thus providing objective samples to eval-uate the pure GNRH-a effects. However, ART group with short S.C.

GnRH-a use showed decreased integrin staining intensity (HSCORE p:0.62)which may be attributable to the effects of follicular stimulation and alteredhormonal status on the endometrial maturation. Thus we may conclude thatovarian stimulation is the major factor altering the endometrial receptivityin ART than the use of GNRH-a.

Supported by: none.

P-353

Establishment of in vitro maturation system (IVM-IVF) as a routineART procedure by combination of HCG administration and frozen-thawed embryo transfer. Aisaku “Isaac” Fukuda, Yoshiharu Nakaoka,Masatake Tohnaka, Hidetaka Okada, Hirotsugu Oku, Yoshiharu Morimoto.IVF Osaka Clin, Higashi-Osaka City, Japan.

Objective: In vitro fertilization of in vitro matured oocytes (IVM-IVF) ishardly used as a routine ART procedure due to low pregnancy outcome.IVM-IVF is a relatively new method of ART and its methodology should beimproved. However, it has numerous benefits such as less stressful physi-cally, mentally and economically, less time consuming and no risks ofgonadotropins administrated. The present study was conducted to establishIVM-IVF as a standard ART procedure by selecting either fresh or frozen-thawed embryo transfer depending on endometrium thickness at oocyteretrieval and by administrating HCG on previous number of immatureoocytes retrieved.

Design: IVM-IVF was applied on the patients with PCOS or having atleast unilateral ovary appearing PCO like echo image. Repeated IVF failurecases that desired to have this treatment were another indication. Pregnancyoutcomes from Oct 1999 to Dec 2001 were analyzed.

Materials/Methods: Immature oocytes were retrieved when patients hadat least two small follicles more than 8 mm in diameter and before devel-opment of a dominant follicle more than 14 mm. When endometrial thick-ness was 8 mm or more at oocyte retrieval, embryos were transferred infresh cycles. In case of endometrial thickness less than 8 mm, two-pro-nuclear oocytes or cleaved embryos were frozen for future frozen-thawedtransfer in hormone-supplemented cycles. Ten thousand unit of HCG wasadministered 36 hours before retrievals for the patients who did not get morethan 2 eggs. Immature oocytes were cultured for 24 hrs and ICSI wasperformed on matured oocytes. Day three embryos were transferred afterbiochemical assisted hatching either in fresh or in frozen-thawed cycles.Pregnancy outcomes and other parameters were analyzed.

Results: Maturation rate was 43% (870/2018) in 24 hours and 80%(695/870) of matured eggs were fertilized by ICSI. A total of 26 pregnancies(15% per 178 transfers and 17% per 149 patients) were achieved in eitherfresh (17) or frozen-thawed transfer (9). Miscarriage rate was 31% (8/26)overall. As of Jan 2002, 14 normal babies (1 set of twin) were born from 13deliveries. The PCOS patient ratio in pregnant cases from fresh transfer(82%) was significantly higher compared to frozen-thawed transfer cycles(33%). Two pregnancies in fresh transfer were achieved after HCG admin-istration.

Conclusions: IVM-IVF is enrolled into our routine ART program. Thepregnancy rate of IVM-IVF is lower compare to stimulation cycles, but thisrate is acceptable when numerous benefits of unstimulated cycles weretaken into account. The present study suggests that IVM-IVF can be one ofthe routine ART procedures and will be potentially an alternative forstimulation IVF cycles. The development of IVM culture media needs to bestrongly pursued.

Supported by: None.

P-354

Prescribed medications and sperm production and function duringIVF. Lucy Lu, Xavier Sanchez, Cory Look, Joy Lacsamana, ErlindaMacanas, Lewis Krey. Program for IVF, Reproductive Surg & Infertility,New York Univ Medical Ctr, New York, NY.

Objective: Men participating in an IVF cycle often take prescribedmedications whose impact on ART outcome is unreported. Although theinfluences of several medications upon semen parameters have been studiedpreviously, their impact on sperm fertilization ability and resultant embryodevelopment remain unknown. This study evaluates the effects of severalgroups of commonly prescribed medications on sperm production andfunction.

S232 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002

Page 2: Prescribed medications and sperm production and function during IVF

Design: Retrospective analysis of semen analysis results and data fromIVF cycles conducted 1999 through 2001 at a university-based andrologylaboratory and IVF program.

Materials/Methods: Ejaculates from 39 men who underwent routine se-men analysis prior to and while participating in an IVF cycle were evaluatedaccording to WHO criteria. The men were grouped according to the 4different types of medications prescribed: statins, anti-depressants, beta-blockers and sedatives and the following ART data were analyzed: spermcount and motility, fertilization rate (2 pronuclear zygotes/oocytes re-trieved), clinical pregnancy (defined by a gestational sac and fetal heartbeat)rate expressed per retrieval and per patient and numbers of miscarriages.Female partner age (�40 and �40 years) was also factored into consider-ation when analyzing fertilization, pregnancy and miscarriage outcomes.

Results: Semen parameters at the time of IVF did not differ from thosedetermined in a preliminary semen analysis. Enriched sperm preparations(routinely 90�% motility) were prepared and aliquots were added to HTFmicrodrops containing eggs under oil; eggs were checked for normal fer-tilization (2 pronuclei, 2 PN) 16 h later. ICSI was performed for a few malefactor patients as determined by WHO criteria. From 1999 to 2001 theprogram-wide 2 PN fertilization rate averaged 60–70% for inseminationand ICSI. Although the rates were slightly lower in these men, the biologicsignificance of this reduction are likely trivial given the high pregnancyrates observed in all groups. In the statin, anti-depressant, beta-blocker andsedative groups 5, 4, 2 and 3 pregnancies occurred in cycles in which thefemale partner was �40 years of age. Clinical pregnancy loss was unusuallyhigh in the statin treatment group; losses occurred in every cycle in whichthe female partner was �40 years old and 1 patient suffered 2 miscarriages(misc).

Meds # pts# IVFcycles

MeanCount

(motility)

2 PNfert rate(# ICSI)

Clin Preg(�FH) per

patient# misc(# pts)

Statins 14 29 107 (53) 57% (4) 10/14 (71%) 9 (8)Antidepressants 16 23 73 (46) 58% (5) 11/16 (69%) 1 (1)B-Blockers 5 9 82 (51) 57% (0) 4/5 (80%) 0Sedatives 4 5 117 (32) 53% (4) 3/4 (75%) 2 (1)

Conclusions: Previous studies have documented that fertility outcome iscompromised in men taking Ca�� blocking drugs for hypertension. Thepresent data suggest no adverse effects of beta-blockers, sedatives or anti-depressant treatment on the fertility potential of men undergoing ARTprocedures. Although the pregnancy outcome data is encouraging for IVFcycles that utilized fresh sperm from men receiving anti-lipemic treatmentwith statins, the high miscarriage rate is disturbing and warrants closerinspection of the performance of similarly treated men and women in thefuture.

Supported by: N/A.

P-355

Screening of oocyte and semen donors: Are we discriminating againstsperm donors? Panayiotis M. Zavos, Pavlos Aslanis, Khalied Kaskar,Panayota N. Zarmakoupis-Zavos. Andrology Institute of America; Ken-tucky Ctr for Reproductive Medicine & IVF, Lexington, KY; Greek-American Andrology Institute, Athens, Greece.

Objective: The advent of IVF and other advanced assisted reproductivetechnologies has brought about greater demands for gamete donation.Furthermore, the criteria that are currently used or employed for screeningoocyte and sperm donors seem to be deviating from each other because ofsignificant variations in the ways that these gametes are preserved. Mean-while, the ASRM is the only agency that has generated guidelines andrecommendations for screening of gamete donors. The objective of thisstudy was to describe current screening practices as it pertains to sperm andoocyte donations and to compare those screening practices with the ASRMpublished recommendations.

Design: A prospective study collecting data from various gamete dona-tion centers regarding their donor screening requirements and policies.

Materials/Methods: A survey was conducted from ten ART or gametehandling programs that offer either sperm or oocyte donation services. Eachprogram was asked to provide a list of screening tests that their prospectivedonors must undergo to become eligible for donation. Also the frequency of

such screening was compared between sperm and oocyte donor groupsversus the ASRM published recommendations.

Results: There were no major differences in the medical screening testsperformed and the percentage of centers performing these tests for bothsperm and oocyte donors. However, the most apparent difference noted wasin the quarantine period for oocyte donors (0 months) and sperm donors (6months). Also, 90% of the centers tested perform continued screening testson a regular basis (3 or 6 months) for sperm donors, whereas only 10% ofthe oocyte donation centers repeat screening every 6 months. In almost allof the parameters evaluated and compared in this survey, gamete donationcenters performed more or an equal number of tests on sperm donors thanon oocyte donors. There was no apparent difference between the percentageof centers performing genetic screening for sperm (60%) or oocyte donors(70%).

Centers (%) performing various screening tests for sperm and oocytedonors.

Donor Psychological GeneticRepeat

ScreeningFamilyHistory Quarantine

Sperm 50% 60% 90% 100% 6 monthsOocyte 30% 70% 10% 80% 0 months

Conclusions: The results clearly show that there is a difference in thescreening procedures for sperm and oocyte donors, and the frequency oftesting. According to ASRM guidelines for gamete donor screening, noquarantine period is needed for oocyte donors due to the inability tocryopreserve oocytes. The question now arises as to whether the oocytecarries less of a risk of transmitting infectious diseases than sperm, whichare quarantined for at least 6 months before it can be used for insemination.Since the main reason for the 6 month quarantine is due to the “windowperiod” of HIV testing, we propose that the use of PCR technology be usedto quantitatively test for the presence of the HIV virus and does not requirea 6 month waiting period. The ASRM clearly states that “screening for HIVshould be performed using current standards of practice” and in our opinion,since PCR technology is the most advanced, currently available and is usedby various centers, that the guidelines for gamete donation, especially withregards to quarantine periods, should be re-evaluated and reconsideredaccordingly.

Supported by: Andrology Institute of America and The Kentucky Centerfor Reproductive Medicine & IVF.

P-356

Hysteroscopic evaluation of the effect of three different embryo trans-fer catheters on the endometrium. Marcelo Lemgruber, Marcos ACSampaio, Marcello Valle, Selmo Geber. ORIGEN, Ctr de Medicine Re-produtiva, Rio de Janeiro, Brazil.

Objective: Evaluate the effect of 3 different catheters for embryo transferon the endometrium.

Design: Prospective study.Materials/Methods: We studied 9 normally cycling women (age: 32 to 35

years old) submitted to hysteroscopic examination, before starting IVFtreatment. Patients were assigned to one of the 3 groups: Frydman catheterfor easy transfer (Group 1, n�3) Frydman double lumen catheter (Group 2,n�3) and Frydman set catheter for difficult transfer (Group 3, n�3).Diagnostic Histeroscopy was performed on day 16 of the menstrual cycle.A mock embryo transfer was performed and immediately after removing theembryo catheter, the endometrium was evaluated using Storz hysteroscope.The effect on the endometrium was then compared.

Results: In patients of group 1 (Frydman catheter for easy transfer), notrace was observed on the endometrium. All patients of group 2 (Frydmandouble lumen catheter) had a superficial trace on the endometrium, and allpatients of group 3 (Frydman set catheter for difficult transfer) had a deeptrace on the endometrium.

Conclusions: The choice of embryo transfer catheter might affect theoutcome of the IVF treatment as they provoke different effects on theendometrium. Therefore they may influence the process of implantation.

Supported by: None.

FERTILITY & STERILITY� S233