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PubMed2004

The impact of conventional and high-dose therapy for lymphoma on fertility.

The impact of chemotherapy on gonadal function is an important issue for younger patients surviving lymphoma. This article reviews the effects on fertility of conventional and intensive-dose chemotherapy regimens with or without radiation therapy. In general, conventional dose regimens such as ABVD (doxorubicin/bleomycin/vinblastine/decarbazine) and CHOP21 (cyclophosphamide/doxorubicin/vincristine/prednisone) are not sterilizing, but data are limited on the effects of newer aggressive regimens such as BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone), CHOP14, and CHOP/etoposide. Infertility after myeloablative transplant conditioning is common but not invariable. The role of prechemotherapy gonadotrophin-releasing hormone agonists and antagonists for the prevention of gonadal damage is under evaluation. In addition, new techniques for sperm and oocyte retrieval offer the prospect of improved fertility after sterilizing treatment. Management guidelines for patients undergoing nonmyeloblative and myeloablative therapy are presented, addressing additional issues such as contraception during and after the administration of cytotoxics and the importance of gynecologic and endocrine follow-up in determining the need for short- and long-term hormone replacement therapy.

Antineoplastic Agents↗
PubMed1999

[Etiology and treatment of sterility due to azoospermia].

Azoospermia can be classified according to the serum level of FSH into obstructive (OA) or non-obstructive (NOA) azoospermia. It can also be due to a lack of gonadotrophins. In the latter case the administration of FSH and HCG can normalize the sperm production. In the other cases ICSI must be performed. In OA sperm can be retrieved using percutaneous epididymal aspiration or testicular fine needle aspiration in case of failure of vasovasostomy or epididymovasostomy. In NOA or spermatogenic arrest, focal spermatogenesis can be observed in 40 to 50% of cases using repeated testis biopsies, allowing to perform ICSI. Although the risk of malformation in children born after ICSI is not increased there is an increased risk to transmit genetic abnormalities in case of NOA (such as the rate of sex chromosome, or microdeletions of the Y chromosome) and in case of congenital OA (mutations of the cystic fibrosis gene).

Chorionic Gonadotropin↗
PubMed2000

Apoptosis in human cumulus cells in relation to maturation stage and cleavage of the corresponding oocyte.

BACKGROUND: The purpose of this study was to determine the incidence of apoptosis in cumulus cells, and correlate these findings with the maturation stage, fertilization rate and embryo score of the corresponding oocyte, in couples undergoing ICSI due to a male factor. METHODS: The study group consisted of 21 couples where ICSI was performed. The total number of oocyte-cumulus complexes retrieved was 164. Sperm samples were assessed according to the WHO manual, morphology according to the strict criteria and for the presence of apoptosis. The degree of apoptotic DNA fragmentation was determined using the free 3'OH DNA termini in situ with chemically labeled and unlabeled nucleotides. The study was blinded for the technician involved in the assessments of apoptosis in the cumulus cells, apoptosis and morphology in spermatozoa. Ovarian hyperstimulation was carried out according to a long down regulation protocol using GnRH, recFSH and hCG. A maximum of 3 embryos were transferred on day 2 after ICSI. RESULTS: This study demonstrated that the incidence of apoptosis was significantly higher in cumulus cells from germinal vesicle and metaphase I oocytes compared to cumulus cells from metaphase II oocytes (p<0.0001). Non-fertilized metaphase II oocytes showed significantly higher incidence of apoptosis in cumulus cells compared to fertilized metaphase II oocytes (p=0.0082). Furthermore, apoptosis in spermatozoa had an impact on the embryo score (p=0.0087). CONCLUSION: Comparing apoptosis in cumulus cells with maturity of the corresponding oocytes, a significantly higher degree was found related to immature oocytes. Apoptosis in cumulus cells from human metaphase II oocytes impaired the fertilization rate. The degree of fragmentation in the embryo might be correlated to apoptosis in the spermatozoa.

Adult↗
PubMed1999

Correlation between the motility of frozen-thawed epididymal spermatozoa and the outcome of intracytoplasmic sperm injection.

The purpose of this study was to investigate if the outcome of ICSI was influenced by epididymal sperm motility in frozen-thawed specimens. A total of 18 ICSI treatment cycles using spermatozoa retrieved by microsurgical epididymal sperm aspiration (MESA) were analysed retrospectively. Cryopreservation of epididymal spermatozoa was performed when enough epididymal aspirates were collected. Sixty-nine out of 126 oocytes injected with spermatozoa retrieved by MESA were fertilized, giving a fertilization rate of 54.8%. Out of 18 embryo transfer cycles, 6 (33.3%) achieved pregnancies. Fresh epididymal spermatozoa were used in 5 cycles while frozen-thawed epididymal spermatozoa were used in 13 cycles for ICSI. The fertilization rates were 68.6% (35/51) in the former group and 45.3% (34/75) in the latter group, respectively. There was a significant difference between the two groups (p < 0.05). In ICSI treatments using fresh epididymal spermatozoa, the cells used for injection were all motile. However, motile epididymal spermatozoa could be used in only five ICSI treatment cycles after freeze-thawing. In 6 cycles, only immotile sperm were used for injection of frozen-thawed spermatozoa. The fertilization rate in each group was 68.4% (13/19) and 31.6% (12/38), respectively. There was a significant difference between these groups (p < 0.01). These results indicate that the outcome of ICSI was influenced by sperm motility in frozen-thawed epididymal specimens. When no sperm motility could be recovered after freeze-thawing even with chemical treatments, consideration should be given to retrieving fresh epididymal spermatozoa again to achieve a better fertilization rate in such patients.

Epididymis↗
PubMed2005

Influence of motility and vitality in intracytoplasmic sperm injection with ejaculated and testicular sperm.

The vitality of spermatozoa used for intracytoplasmic sperm injection (ICSI) is a crucial factor for fertilization, establishment and outcome of a pregnancy in assisted reproductive technique cycles. The sperm origin may also be a limiting factor, although little is known about this issue. It is known that the motility of injected spermatozoa and their origin from ejaculate or testicular biopsies are important predictors in terms of fertilization, pregnancy and birth rates. Oocytes of patients in 2593 cycles were retrieved in our in vitro fertilization programme and inseminated via ICSI. We used motile (group 1, n = 2317) or immotile ejaculated spermatozoa (group 2, n = 79), motile sperm retrieved from testicular biopsies (group 3, n = 62) and immotile spermatozoa from testicular biopsies (group 4, n = 135). Female age and number of oocytes retrieved did not differ significantly among the groups. The fertilization rates were as follows: 67.1% in group 1, 49.8% in group 2, 68.3% in group 3 and 47.8% in group 4. The pregnancy rates in cases where three embryos had been transferred amounted to 35.7% in group 1, 17.3% in group 2, 38.3% in group 3 and 20.5% in group 4. The embryo quality showed no differences between groups 1 and 3 (14.5), and between groups 2 (11.8) and 4 (10.8). The abortion rate was similar in groups 1-3, but increased in group 4 (26.6%, 27.3%, 31.6% and 55.5%). Irrespective of their origin, the fertilization potential of injected spermatozoa was found to be influenced by motility. The resulting pregnancy and birth rates, i.e. the potential of the resulting embryos to implant and to achieve viable pregnancies, seem to be additionally dependent on the sperm origin. This was well shown by declining rates when spermatozoa in a relatively early stage of maturity had been used. We see increasing evidence that the degree of sperm maturity has an important impact on the outcome of ICSI. In obstructive azoospermia, spermatozoa retrieved from the epididymis should be used rather than testicular biopsy spermatozoa, or testicular sperm should be preincubated in culture medium before ICSI.

Adult↗
PubMed2000

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta.

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.

Adult↗
PubMed2006

Correlation between number of retrieved oocytes and pregnancy rate after in vitro fertilization/intracytoplasmic sperm infection.

The implementation of safe and maximally effective ovarian stimulation is a major aim for in vitro fertilization (IVF) teams. The goal of controlled ovarian hyperstimulation (COH) is to supply enough oocytes with normal maturation to insure the consequent biological procedures. A variety of different stimulation protocols have been suggested and an individual selection of the correct stimulation protocol is mandatory. The aim of the present study is to evaluate the correlation between number of retrieved oocytes and clinical pregnancy rate (CPR) after IVF or intracytoplasmic sperm injection (ICSI) procedures. We reviewed 1017 cycles in a total of 975 patients. The study results clearly demonstrate that the aspiration of less than 5 oocytes significantly reduced pregnancy rate. The aspiration of a large number of oocytes (>15) does not lead to an increase of the treatment effect and, at the same time, increases the risk of ovarian hyperstimulation syndrome. The major goal is to obtain 5-15 oocytes as a "gold standard", connected to optimal pregnancy rate after assisted reproduction (ART).

Adult↗
PubMed1998

Double oocyte aspiration may be a solution for empty follicle syndrome: case report.

OBJECTIVE: To assess the possibility of salvaging the cycle in a case of empty follicle syndrome by scheduling a second retrieval. SETTING: Miami IVF/Intracytoplasmic Sperm Injection Center, Alexandria, Egypt. It is a private center. PATIENT(S): A 24-year-old female with a 6-year history of primary infertility. Intracytoplasmic sperm injection was performed because of her partner's obstructive azoospermia. No oocytes could be retrieved despite normal ultrasonic and hormonal responses and the presence of 25 mature follicles. INTERVENTION(S): Serum hCG on the day of the first retrieval. A second dose of hCG was given after the first retrieval, and a second retrieval was scheduled 24 hours later. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, fertilization and cleavage rates, and pregnancy outcome. RESULT(S): Serum beta-hCG level on the day of the first retrieval was 300 IU/mL. Eleven oocytes were retrieved, (7 were metaphase II, 3 fertilized, and 2 cleaved) and two embryos were transferred. No pregnancy resulted. CONCLUSION(S): In a variant of empty follicle syndrome, the cycle could be salvaged by giving another dose of hCG and scheduling another retrieval 24 hours later.

Adult↗
PubMedDate not supplied

[The value of donor sperm in intra-cytoplasmic sperm injections? The French Centers for Semen Preservation policy].

Some IVF laboratories ask for donor's semen during an ICS attempt if retrieval of husband's sperm is unsuccessful. The French Centers for Semen preservation (CECOS) consider that this request is not acceptable for legal, psychological and ethical considerations. Legal consent may not be ambiguous. The psychological lost of biological fatherhood should be totally assumed before undertaking conception with donor's semen. ICSI should be started only if it is most likely to succeed. For all these reasons, CECOS refuse to modify the strategy of procreatione during the course of an attempt.

Ethics, Medical↗
PubMed2000

Sexual assault under benzodiazepine submission in a Paris suburb.

Sexual assaults under benzodiazepine submission have been described, since use of benzodiazepine enables non consensual sexual activity but rarely fully reported. An accurate evaluation of the phenomenon has seemed interesting. Files of 23 adult males and females examined at the Emergency Forensic Unit of an University Teaching Hospital near Paris were reviewed. All the victims had complained from sexual assault under drug submission, in the years 1996 and 1997. A complete examination for sexual assault was realised linked to clinical examination of drug intoxication. Every victim of rape under drug submission was sampled for urine screening (mean delay of 17.5 h after sexual assault) and blood alcohol level quantification. Urine was screened for benzodiazepines, cocaine, opiates and cannabinoids with qualitative immunochromatographic test. Traumatic lesions of sexual penetration were retrieved in 10 victims and sperm in 5. Clinical signs of benzodiazepine intoxication were retrieved in 12 out of 23 victims. Urine benzodiazepine screening was positive, over the cut-off values (300 ng/mL)when sampled less than 20 h after the facts. In 6 out of 23 victims, drugs of abuse and alcohol were associated to benzodiazepines. A reinforced attention can be brought to the rape under drug submission including the need of a proper examination and samplings shortly after the alleged facts to ascertain the diagnosis and to help the victim facing the Justice inquiry.

Adolescent↗
PubMed1997

Percutaneous vasal sperm aspiration and intrauterine insemination in the treatment of obstructive azoospermia.

OBJECTIVE: To treat obstructive azoospermia by using sperm recovered from percutaneous vasal sperm aspiration in IUI. DESIGN: Clinical study. SETTING: Institutional clinic in Jinan. PATIENT(S): Six men with obstructive azoospermia, three of whom were treated with percutaneous vasal sperm aspiration and IUI; sperm recovered from this procedure were used for IUIs. INTERVENTION(S): Spermatozoa used for intrauterine injection were retrieved by percutaneous vasal sperm aspiration and incubated at 37 degrees C for 40 to 60 minutes. MAIN OUTCOME MEASURE(S): Normal pregnancy. RESULT(S): Intrauterine insemination was performed in three patients for one or two cycles, with motile spermatozoa. There was one successful term delivery. CONCLUSION(S): Percutaneous vasal sperm aspiration can be used successfully to recover sperm in men with obstructive azoospermia for use in IUI. The technique is simple and less traumatic than an open surgical procedure.

Female↗
PubMed2005

Testicular fine needle aspiration as a diagnostic tool in non-obstructive azoospermia.

AIM: To report the fine needle aspiration cytology (FNAC) of the testes used as a diagnostic tool in non-obstructive azoospermic patients. METHODS: One hundred and twenty-five non-obstructive azoospermic male candidates to intracytoplasmic sperm injetion (ICSI) were analysed for follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and inhibin B plasma levels. They were classified into three groups on the basis of FNAC: 1) Sertoli cell-only syndrome (SCOS) (70); 2) severe hypospermatogenesis (42); and 3) maturation arrest (13). Then, all men underwent testicular sperm extraction (TESE) for sperm recovery for ICSI. RESULTS: Mature spermatozoa were detected by FNAC in 24 of 42 men with severe hypospermatogenesis and nine of 13 men with maturation arrest; while they were retrieved by TESE in 29 of 70 men with SCOS, 35 of 42 men with severe hypospermatogenesis (including the 24 by FNAC) and 10 of 13 men with maturation arrest (including the nine by FNAC). The sensitivity and specificity of FNAC were 44.6 % and 100 %, respectively. There was no difference on testicular volume and hormonal parameters in men with and without sperm retrieved. CONCLUSION: These findings suggest that FNAC may be a simple and valid diagnostic parameter in non-obstructive azoospermic men and it may represent a valid positive prognostic parameter for sperm recovery at TESE.

Adult↗
PubMed1997

Sperm count in ejaculates and after sperm selection with discontinuous percoll gradient centrifugation technique, as a prognostic index of IVF outcome.

Success of IVF with low sperm count will depend on the retrieval of the maximum number of normal motile sperms, and this makes the selection of an appropriate technique critical. Various in vitro methods have been developed for selecting human sperm cells. Sperm selection using percoll gradient has been reported to yield upto 60% motile and morphologically normal spermatozoa from a normal semen sample. In this study, we have attempted to determine a possible relationship between sperm count in ejaculates before and after selection with percoll gradient centrifugation on one hand, and fertilization, cleavage and pregnancy rates in an IVF program on the other. With increased sperm count at the time of IVF treatment using selected sperm, we observed higher fertilization, cleavage and gestational rates. In conclusion, sperm concentration before and after selection with percoll may be considered a prognostic parameter for the determination of fertilization potential and pregnancy rates in an IVF program.

Cell Division↗
PubMed2002

Posthumous reproduction: current and future status.

Posthumous reproduction became possible with the technologies of sperm cryopreservation and ART. The legal and social status of children born as a result of these technologies continue to evolve. The proper disposition of unwanted stored gametes and embryos remains unknown. Physicians are increasingly asked to make quick judgments on posthumous gamete retrieval. The procedures for gamete harvest are technically simple; however, one must carefully select cases with definitive prior intent to have children. There is a need for standardized legal protocols to protect the physician and the patient. The physician must use sound judgment and comply with accepted standards, when present, before performing any service for posthumous sperm retrieval and reproduction.

Female↗
PubMed1993

Assessment of human sperm functional changes after in-vitro coincubation with cells retrieved from the human female reproductive tract.

Human spermatozoa must undergo functional changes prior to fertilization; however, the site of this physiological event is still unclear. To evaluate the influence of the female reproductive tract on sperm fertilizing capacity, fertile sperm samples were coincubated with endometrial, oviductal, granulosa and cumulus cells, follicular fluid and maternal serum. Sperm penetration into the zona-free hamster ova and motion parameters were measured daily for 72 h. Compared to control samples, endometrial and oviductal cell cultures did not alter sperm fertilizing capacity or their movement characteristics. Sperm coincubated with follicular fluid, granulosa or cumulus cells exhibited a significantly higher ability to penetrate zona-free hamster ova for up to 48 h. Sperm motility increased at 4 h in the presence of follicular fluid and serum. At 24 h sperm velocity and amplitude of lateral head displacement significantly declined in sperm samples exposed to serum, and velocity also declined in follicular fluid and with coincubation using ovarian follicle cells. Sperm motility and velocity decreased at 48 h in the presence of serum, follicular fluid, cumulus or granulosa cells. Our findings may suggest that specific secretory factors produced in the human pre-ovulatory ovarian follicle enhance human sperm fertilizing capacity.

Adult↗
PubMed1998

Perivitelline space granularity: a sign of human menopausal gonadotrophin overdose in intracytoplasmic sperm injection.

The significance of the presence of coarse dark granules in the perivitelline space of oocytes has not been studied before. The study included 2288 intact oocytes [2063 in metaphase II (MII), 136 in metaphase I (MI), and 89 in germinal vesicle (GV)] retrieved in 206 intracytoplasmic sperm injection cycles stimulated by a long agonist protocol. The incidence of granules varied with oocyte maturity. It was detected in 34.3% and 4% of the MII and MI oocytes respectively, while none of the GV oocytes contained granules. The woman's age, hormonal values (oestradiol and progesterone), human chorionic gonadotrophin/oocyte retrieval interval, number of oocytes retrieved, and oocyte retrieval/injection interval were not related to the percentage of granular oocytes. Moreover, there was no correlation between the percentage of granular oocytes and the fertilization and cleavage rates, pregnancy outcome, as well as the implantation rate. Patients were divided into three groups according to the total human menopausal gonadotrophin (HMG) dose they received. There was a statistically significant difference between the three groups in the percentage of granular oocytes [17.4 +/- 5.2% versus 26.7 +/- 3.2% versus 45.4 +/- 4.2% in the low-dose (< 30 ampoules), intermediate dose (31-45 ampoules), and high-dose (> 45 ampoules) groups respectively]. We conclude that granularity in the perivitelline space is probably a physiological phenomenon related to the maturational events in oocytes and enhanced by exposure to high dosages of HMG.

Adult↗
PubMed1999

[Limitations of reproductive medicine from an andrological/urological point of view].

Since the first child was born after in-vitro fertilization in 1978, different techniques of ovarian stimulation, oocyte retrieval and embryo culture have improved significantly. The development of microinjection techniques was a mile stone in reproductive medicine. Even in cases of severe impairment of semen quality, using the Intracytoplasmic Sperm Injection (ICSI), pregnancy rates of approximately 20 % per treatment cycle can be achieved. However for using artificial reproductive techniques (ART) the female age is a major limiting factor as well as the development of premature ovarian failure (POF). Crucial for the male is the question whether or not sperm cells can be retrieved. Today an interdisciplinary approach is recommended to take care of the afflicted couple in order to address the complex problem of infertility. There is evidence that children born after microinjection techniques bare a higher risk for chromosomal aberrations compared to the normal population. However rates of major malformations seem to be identical in both groups. An evaluation of the potential risks and efforts and an extensive counseling of the infertile couple has to be taken before initiating invasive ART.

Chromosome Aberrations↗
PubMedDate not supplied

Evaluation of ICSI-selected epididymal sperm samples of obstructive azoospermic males by the CKIA system.

The objective of this study was to evaluate nuclear normality in intracytoplasmic sperm injection (ICSI)-selected epididymal sperm from obstructive azoospermic (OA) patients. We evaluated whether the selection criteria used in routine ICSI (morphology and motility at a magnification of 400x) is adequate for selecting "normal" sperm from epididymal samples. Surgically retrieved spermatozoa from the caput epididymis of 15 OA patients and ejaculated sperm samples from 9 normospermic donors were evaluated with a DNA-specific stain (Feulgen) and in combination with the computerized karyometric image analysis (CKIA) system. Original (unselected) samples and ICSI-selected sperm were compared in donor and patient samples. In the original fraction, a larger variation in almost all measured parameters was found in epididymal sperm than in ejaculated sperm. After sperm selection, the morphometry was comparable between epididymal and ejaculated sperm. However, for those parameters related to the DNA stainability and chromatin texture (nuclear condensation), significant differences between patients and donors were observed. This result suggests that the size and form of the sperm do not necessarily hold similar internal structures. Thus, the frequency of "normal" sperm significantly increased after ICSI selection, but the improvement was more marked in donor than in OA patients' samples. In conclusion, at least a twofold increase in the number of normal spermatozoa was achieved after ICSI selection. The heterogeneity in the stainability and chromatin condensation of epididymal samples from OA patients indicates that some of the selected spermatozoa have a hypocondensed or hypercondensed chromatin. Even in the best of donor cases, no more than 55% of the selected sperm scored normal with CKIA, indicating that the present routine ICSI selection criteria are not sufficient for selecting normal condensed nuclei.

Ejaculation↗