Incidence of chromosomal aberrations in children born after assisted reproduction through intracytoplasmic sperm injection.
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Child↗
Biomedical subjects
P Devroey
Publications and source records attributed to P Devroey.
Intracytoplasmic sperm injection, results in women older than 39, according to age and the number of embryos replaced in selective or non-selective transfers.
The aim of this study was to assess the results of intracytoplasmic sperm injection (ICSI) in a large cohort of women older than 39 according to age and to embryo transfer policy. In all, 736 ICSI cycles were analysed retrospectively. In 576 (78.3%) cycles an embryo transfer was carried out. The embryo transfer was defined as non-selective when all the available embryos were transferred, and as selective when fewer than the available number of embryos were replaced. A statistically significant gradual decrease in the number of embryos available for transfer, the number of good or excellent quality embryos available for transfer, the pregnancy rates, the clinical pregnancy rates, the implantation rates and the viable pregnancy rates was found with advancing age. No viable pregnancies ensued in women from 45 years old onwards. There was a statistically significant gradual increase in the pregnancy rates, the clinical pregnancy rates, the implantation rates and the viable pregnancy rates from non-selective to selective transfers. The results were similar in women with five or more embryos available, irrespective of the embryo transfer policy. It seems, therefore, that the ovarian reserve and the chances for a successful pregnancy decrease gradually with advancing age, and it is pointless to treat women from 45 years old onwards. A subgroup of patients with better ovarian response and more embryos available for transfer have higher chances of conception. Conception and implantation rates depend mainly on the quality of the transferred embryos. However, the implantation capacity of the embryos is generally lower irrespective of their good morphology.
Adult↗
Correlation between motility of testicular spermatozoa, testicular histology and the outcome of intracytoplasmic sperm injection.
The objective of the present study was to analyse the influence of motility on the results of intracytoplasmic sperm injection (ICSI) when testicular spermatozoa are used for microinjection and to correlate this with testicular histology. A total of 197 ICSI treatment cycles (167 couples) was analysed retrospectively in which testicular spermatozoa were used, because of complete azoospermia, for microinjection. Fertilization, embryo cleavage, transfer and pregnancy rates were evaluated and compared in relation to motility of testicular spermatozoa. In 170 cycles, histological diagnoses were compared with findings on motility. Injection of motile testicular spermatozoa (in 159 cycles) provided a higher normal fertilization rate than did injection of non-motile spermatozoa (in 14 cycles; 65 versus 45% respectively). Normal spermatogenesis was diagnosed in a significantly higher proportion and incomplete maturation arrest in a significantly lower proportion in the group of patients in which only motile spermatozoa were used for microinjection (65 and 10%), as compared to the group where exclusively non-motile spermatozoa were used (36 and 36%). Fertilization rate after ICSI was relatively high when non-motile testicular spermatozoa were used for microinjection, but use of motile testicular spermatozoa was associated with a still higher fertilization rate (except when histology of the testicular biopsy showed normal spermatogenesis), and therefore selection of motile testicular spermatozoa is always preferable for ICSI. Normal spermatogenesis predicts a greater probability, and maturation arrest a lower probability of recovering motile testicular spermatozoa.
Cytoplasm↗
Fine needle aspiration versus open biopsy for testicular sperm recovery: a controlled study in azoospermic patients with normal spermatogenesis.
This retrospective controlled study aimed at comparing two techniques for recovering testicular spermatozoa in azoospermic patients undergoing intracytoplasmic sperm injection (ICSI). 102 men suffering from infertility because of obstructive azoospermia had ICSI using testicular spermatozoa recovered either by open excisional biopsy (n = 51), or by fine needle aspiration (FNA) (n = 51). A higher average number of spermatozoa were recovered after open biopsy than after FNA, but no significant differences in either fertilization rates or cleavage rates were observed after ICSI with spermatozoa retrieved by the two techniques. Neither was there any significant difference in ongoing pregnancy and implantation rates: in the FNA group, these figures were respectively 19.6% per cycle and 7.8% per embryo transferred and in the open biopsy group 21.6 and 7.1%. We conclude that ICSI with testicular spermatozoa recovered by FNA yields results comparable to those obtained with spermatozoa recovered by open biopsy in azoospermic patients with normal spermatogenesis. However a prospective study is needed to confirm the present results and to assess recovery rates and patient comfort for the two methods.
Biopsy↗
Hysteroscopic septum resection in patients with recurrent abortions or infertility.
Fifty-seven patients who underwent hysteroscopic septum resection between January 1991 and December 1996 were studied; nine patients presented with recurrent abortions, 46 with infertility (26 primary and 20 secondary), one with dysmenorrhoea and one with an asymptomatic complete septum. Their reproductive history included 78 pregnancies: 69 (88.4%) abortions, two (2.6%) ectopics, two (2.6%) preterm deliveries and five (6.4%) term deliveries. In patients with infertility, the incidence of unexplained infertility was 19.6% and the incidence of endometriosis was 26.1%. After hysteroscopic septum resection, 42 patients were interested in pregnancy. All patients with recurrent abortions conceived spontaneously. Twenty-one (63.6%) infertile patients achieved a pregnancy, 13 (61.9%) of them after treatment with various assisted reproduction techniques. The reproductive outcome after septum resection yielded 44 pregnancies, including three sets of twins and one set of triplets reduced to twins: 11 (25%) abortions, one (2.3%) ectopic pregnancy, two (4.5%) preterm deliveries (both twins), 28 (63.7%) term deliveries and two (4.5%) as-yet ongoing pregnancies. It seems that the hysteroscopic treatment of uterine septum has a beneficial effect on pregnancy outcome. A septate uterus does not seem to be an infertility factor. The achievement of pregnancy is normal in patients with recurrent abortions, while the chances of conception in patients with infertility seem to be similar to those for the general infertile population.
Abortion, Habitual↗
Testicular sperm extraction and intracytoplasmic sperm injection.
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Cytoplasm↗
Comparison of assisted reproductive technology performance after oocyte retrieval under general anaesthesia (propofol) versus paracervical local anaesthetic block: a case-controlled study.
Propofol (Dipirivan) is an intravenous anaesthetic drug used for general anaesthesia. Although frequently used as a general anaesthetic for ultrasound procedures, its use during transvaginal oocyte retrieval is currently being debated. A total of 202 patients undergoing fertility treatment was included in a prospective, matched, controlled study, in which we compared fertilization rates and embryo development in terms of morphological quality and speed of development and the implications for reproductive outcome and pregnancy following general anaesthesia using either propofol or a paracervical local anaesthetic block during oocyte collection. There were no differences between the fertilization rates and the embryo cleavage characteristics for the two groups. The initial implantation rate per transferred embryo after general anaesthesia was similar to that after paracervical local anaesthetic block (13.4 versus 18.6%; P = 0.10). The ongoing clinical implantation rates per embryo transferred were also similar in the two groups.
Adult↗
Results of intracytoplasmic sperm injection with ejaculated, fresh and frozen-thawed epididymal and testicular spermatozoa.
Over the past 5 years, intracytoplasmic sperm injection (ICSI) has been developed to alleviate severe long-standing andrological infertility in couples who could not be helped by standard in-vitro fertilization (IVF), or who could not undergo IVF because too few motile and morphologically normal spermatozoa were present in the ejaculate. ICSI can also be carried out with fresh and frozen-thawed epididymal spermatozoa from patients with obstructive azoospermia and with testicular spermatozoa from most patients with obstructive azoospermia and from some patients with non-obstructive azoospermia. This review reports the results of 5 years of ICSI practice (1991-1995) at the Brussels Free University Centre for Reproductive Medicine, including selection of patients, oocyte and spermatozoa for ICSI, ICSI procedures and its assessment. ICSI was performed in 97% of the 4688 planned treatment cycles. Ejaculated spermatozoa were used in 88% of the cycles, epididymal spermatozoa in 5% of the cycles and testicular spermatozoa in 7% of the cycles. ICSI was performed on 48393 metaphase II oocytes. Of these, 89.5% were morphologically intact, and 70.9% of the intact oocytes were normally fertilized; 64.9% of the two-pronuclear oocytes developed after a further 24 h of in-vitro culture into cleaved embryos, which were transferred or cryopreserved for subsequent use. After transfer of fresh embryos, the percentage of cycles with positive serum human chorionic gonadotrophin was 36.2% per transfer and the percentage of deliveries was 27.0% per transfer. The performance of ICSI with regard to damage, pronuclear status, embryo development and transfer was analysed separately for the four different types of spermatozoa used: fresh ejaculated, epididymal and testicular as well as frozen-thawed epididymal spermatozoa.
Cryopreservation↗
Do we treat the male or his gamete?
The history of the male infertility patient is of utmost value. A physical examination is mandatory when psychosexual and ejaculatory dysfunction and male accessory gland infection are suspected, and even in the presence of azoospermia. It is also advisable to perform a physical examination to exclude the presence of testicular tumours. The diagnostic assessment includes sperm analysis, history, physical examination, the Valsalva manoeuvre, Doppler, ultrasonography, hormonal serum measurements, evaluation of testicular volume by orchidometry and evaluation of testicular consistency by palpation. The diagnosis of male infertility is descriptive and determination of true causality is almost non-existent. For decades, various therapies have been proposed to improve sperm parameters in cases of male factor infertility. Administration of anti-oestrogens and androgens is ineffective. No peer-review data are available to demonstrate the benefit of the use of intrauterine insemination or the correction of varicocele. Classic in-vitro fertilization is to some extent a solution for male factor infertility; however, the two-pronuclear fertilization rate for patients with impaired semen samples is significantly lower than that for patients with non-male indications. Conventional treatment for male factor infertility has little value and has been revised and abandoned. Intracytoplasmic sperm injection is an effective treatment, even for cases of extreme oligoasthenoteratozoospermia. It has to be considered the method of choice and should replace ineffective conventional therapies.
Estrogen Antagonists↗
Clinical experience with preimplantation genetic diagnosis and intracytoplasmic sperm injection.
Preimplantation genetic diagnosis (PGD) is a novel procedure whose use may be considered to obtain a very early prenatal diagnosis for couples at risk for transmitting genetic diseases. Using the polymerase chain reaction (PCR) or fluorescence in-situ hybridization (FISH) the genotype or the sex of biopsied cleavage-stage embryos obtained after in-vitro fertilization can be determined and selected embryos can then be transferred. In-vitro fertilization with intracytoplasmic sperm injection is the method of choice to obtain embryos to be analysed through PCR to reduce contamination by residual sperm DNA. In our series of 61 PGD cycles for 29 couples at risk over a period of 4 years the ongoing pregnancy rate per cycle was 15%, per transfer 19% and per patient 31%. One of the six morphologically normal children born, who is still alive and doing well, weighed 850 g after birth at 25 weeks following a complicated triplet pregnancy. More experience is needed to correctly evaluate the efficiency and safety of this novel technique as well as to determine its place in the prevention of genetic disease.
Adult↗
A follow-up study of children born after intracytoplasmic sperm injection (ICSI) with epididymal and testicular spermatozoa and after replacement of cryopreserved embryos obtained after ICSI.
The aim of this prospective follow-up study of children born after intracytoplasmic sperm injection (ICSI) was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones in order to evaluate the safety of this new technique. The study design included karyotyping of the parents and their agreement to genetic counselling and prenatal diagnosis and it was based on a physical examination of the child at the Centre for Medical Genetics at the ages of 2 months, 1 year and at 2 years, where major and minor malformations and psychomotor evolution are recorded. Here we describe the first 57 children born from 40 ICSI pregnancies with epididymal spermatozoa (group 1), the first 50 children born from 34 ICSI pregnancies with testicular spermatozoa (group 2) and the first 58 children born from 48 pregnancies after replacement of cryopreserved ICSI embryos (group 3). Parental karyotypes were obtained from only 72/246 (29%) parents and were all normal. Prenatal karyotypes were determined for a total of 70 samples (40%): 21 in group 1, 15 in group 2 and 34 in group 3. In this last group 2 abnormal 47,XXY karyotypes (5.8%) and no structural aberrations were found. This increase in de-novo sex-chromosomal aberrations has already been described with regard to the first 877 children born after ICSI carried out at our Centre and is probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself. Major malformations, defined as those causing functional impairment or requiring surgical correction, were observed in four children: two born after ICSI with epididymal spermatozoa, one after ICSI with testicular spermatozoa and one after ICSI and cryopreservation. No particular malformation was disproportionally frequent. In the follow-up examinations at 2 months (107/161 or 66.5%) and at 1 year (37/161 or 22.9%), no additional anomalies were observed. Lost for follow-up rate at 2 months was 33.5%. These observations on a limited number of children do not suggest a higher incidence of diseases linked to imprinting, nor do they suggest a higher incidence of congenital malformations. These observations are still limited in number and should be further completed by others and by collaborative efforts. In the meanwhile patients should be told about the available data before any treatment: there appears to be some risk of transmitted chromosomal aberrations, of de-novo, mainly sex-chromosomal aberrations and of transmitting fertility problems to the offspring. Patients should also be reassured that until now there seems to be no higher incidence of congenital malformations in children born after ICSI with epididymal or testicular spermatozoa or after replacement of ICSI embryos.
Adult↗
Clinical application of new micromanipulative technologies to treat the male.
Traditional treatments of the male have produced no improvement in sperm parameters. Since the rate of normal fertilization rate is significantly lower in these cases after classic in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) has become the preferred method of treatment. It has been successfully applied in cases of extreme oligoasthenoteratozoospermia, and obstructive and non-obstructive azoospermia. Cryopreservation of testicular tissue will replace the repeated use of fresh testicular tissue. Full information has to be provided to patients about the frequency (approximately 3%) of sex chromosome and autosomal aberrations in men with extreme oligoasthenoteratospermia. The need for screening for Yq deletions is still under study, and any therapeutic consequences for the newborn child will have to be analysed. The incidence of major malformations in newborn children is approximately 2.5%, i.e. comparable with that of the general population. Screening for de-novo sex chromosome aberrations may be particularly useful for men with sperm counts of < 5 x 10(6) and those with non-obstructive azoospermia.
Adult↗
The predictive value of uterine artery blood flow measurements for uterine receptivity in an intracytoplasmic sperm injection program.
OBJECTIVE: To assess whether uterine artery blood flow impedance, measured as the pulsatility index on the day of ET in patients undergoing IVF-ET with microinjection, can predict the likelihood of pregnancy. DESIGN: Prospective clinical study. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Seventy patients undergoing intracytoplasmic sperm injection (ICSI) for andrologic indications. INTERVENTION(S): Transvaginal color Doppler examination performed on the day of ET. MAIN OUTCOME MEASURE(S): Mean (+/- SD) pulsatility index value of the left and right uterine arteries, serum E2 levels, implantation rates, and ongoing pregnancy rates (PRs). RESULT(S): The patients were divided into pregnant and nonpregnant groups and were separated according to whether the pulsatility index was low (1.00-1.99), medium (2.00-2.99), or high (> or = 3.00). The pulsatility index values did not change statistically in the pregnant and nonpregnant groups. The implantation rates were 19.5%, 15.4%, and 25% for the low-, medium-, and high-pulsatility index groups, respectively. The ongoing PRs for the same groups were 35.3%, 26.7%, and 37.5%, respectively. CONCLUSION(S): The study suggests that blood flow, measured as the pulsatility index on the day of ET, cannot predict the likelihood of pregnancy in stimulated cycles of ICSI.
Arteries↗
Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase.
OBJECTIVE: To investigate the effect of subtle serum P rise before hCG administration on endometrial maturation in stimulated cycles. DESIGN: Case-control study. SETTING: Tertiary referral center. PATIENT(S): Twenty patients with serum P < or = 0.9 ng/mL (group I) (conversion to SI unit, 3.180), 20 patients with premature P rise (> or = 1.1 ng/mL, group II), and 20 patients with normal serum P (group III). INTERVENTION(S): Patients in groups I and II underwent endometrial aspiration biopsies on the day of oocyte retrieval in the ET cycles themselves. Patients in group III, without endometrial biopsies, were chosen as controls. MAIN OUTCOME MEASURE(S): Comparison of endometrial maturation, correlation between endometrial dating and cumulative P exposure, and/or number of days of P > or = 1.1 ng/mL and comparison of clinical outcome. RESULT(S): Groups I and II showed a secretory activity of the endometrium. In group II, the endometrial dating correlated neither with P exposure nor with the number of days of subtle P rise. Clinical pregnancies were observed in both groups but none in cases with endometrium advanced > 3 days. Similar pregnancy and implantation rates were observed between groups I and III. CONCLUSION(S): These data suggest that an endometrial aspiration biopsy performed on the day of oocyte retrieval may be used to assess endometrial receptivity in patients with serum P rise.
Abortion, Spontaneous↗
Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation.
OBJECTIVE: To assess the minimal effective dose of a GnRH antagonist (Cetrorelix; Asta Medical; Frankfurt, Germany) to prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation (COH) for assisted reproductive technologies. DESIGN: In 69 patients COH was carried out with the association of hMG, starting on day 2 of the menstrual cycle, and a GnRH antagonist (Cetrorelix) was administered from day 6 of the hMG treatment (day 7 of the menstrual cycle) every day up to and including the last day of the hMG injection. In 32 and 30 patients, 0.5 mg and 0.25 mg of Cetrorelix were administered, respectively. Seven patients received 0.1 mg of Cetrorelix. SETTING: Tertiary referral center. RESULT(S): No premature endogenous LH surge occurred in patients treated with 0.5 and 0.25 mg of Cetrorelix, and serum LH concentrations were maintained constantly low during the entire follicular phase in both groups. Follicle-stimulating hormone, LH, E2, and P expressed as area under the curve were similar in both groups. A premature LH surge (18 mIU/mL; conversion factor to SI unit, 1.00) with a concomitant P rise (1.7 micrograms/L; conversion factor to SI unit, 3.180) occurred in one of the seven patients treated with 0.1 mg Cetrorelix; therefore, treatment with this dose was discontinued. CONCLUSION(S): The minimal effective dose of Cetrorelix able to prevent premature LH surge in COH cycles is 0.25 mg administered daily.
Adult↗
An improved treatment procedure for testicular biopsy specimens offers more efficient sperm recovery: case series.
OBJECTIVE: To report an improved sperm recovery procedure from testicular biopsy specimens for intracytoplasmic sperm injection (ICSI). DESIGN: Case series and controlled study. SETTING: Procedures were performed in a tertiary IVF center. PATIENT(S): Nonobstructive azoospermic cases (15 patients) and obstructive azoospermic cases (5 patients). INTERVENTION(S): Intracytoplasmic sperm injection was carried out using testicular sperm isolated from a testicular biopsy specimen either with or without erythrocyte lysing buffer treatment. MAIN OUTCOME MEASURE(S): The time required to collect spermatozoa and the intactness and fertilization and developmental rates of oocytes. RESULT(S): In 7 of the 15 nonobstructive cases, it was possible to perform ICSI when, after shredding of the testicular tissue, no (or virtually no) sperm were present. There was no difference in the fertilization rates (83% and 68%) and developmental rates (87% and 89%) of the 54 sibling oocytes from another 5 patients in whom ICSI was carried out with sperm either treated or not treated with erythrocyte lysing buffer. CONCLUSION(S): Erythrocyte lysing buffer treatment of testicular biopsy specimens enhances the efficiency of sperm collection in those cycles in which spermatozoa are present and does not affect fertilization and embryo development.
Ammonium Chloride↗
Relationship between serum follicle stimulating hormone in the male and standard sperm parameters, and the results of intracytoplasmic sperm injection.
Serum follicle stimulating hormone (FSH) is routinely measured when evaluating the infertile male for intracytoplasmic sperm injection (ICSI). However, among the sperm parameters, only its relationship with sperm concentration is well documented. Few investigations concern the relationship between FSH and sperm motility and morphology, and the results of ICSI. A retrospective study of 316 couples who underwent ICSI was carried out to determine the relationships between serum FSH concentrations in the male and (i) standard sperm parameters_(concentration, motility and morphology) and (ii) fertilization, cleavage, pregnancy and implantation rates after ICSI. There was an inverse correlation with sperm concentration and total motility but no relationship was found with progressive motility and sperm morphology. Neither was any relationship found between serum FSH and fertilization, cleavage, pregnancy and implantation rates, and the results of ICSI. These findings suggest the need to review the routine measurement of serum FSH in the infertile male when ICSI is the planned treatment procedure.
Female↗
Are there any predictive factors for successful testicular sperm recovery in azoospermic patients?
Recovery of testicular spermatozoa from azoospermic patients with testicular failure followed by intracytoplasmic sperm injection (ICSI) is a recent advance in the treatment of male infertility. This study aimed at investigating which parameter(s) may predict successful testicular sperm recovery. We reviewed 395 testicular sperm recovery procedures and analysed the most frequently available parameters for clinical decision-making in azoospermic patients: (i) presence of at least one single spermatozoon in at least one preliminary semen analysis; (ii) maximum testicular volume; (iii) serum follicle stimulating hormone (FSH); and (iv) presence of spermatozoa in the histology of a randomly-taken testicular biopsy. Sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and accuracy were calculated for the above index parameters in different clinically relevant subgroups using receiver operating characteristic (ROC) curves whenever possible. Spermatozoa were always successfully recovered in patients with normal testicular histological findings (n = 173) or hypospermatogenesis (n = 16) but not in some patients with tubular sclerosis (seven out of 18), Sertoli cell-only pattern (55 out of 112) or maturation arrest (39 out of 76). Histopathology was the best test for predicting successful sperm recovery in the whole population (sensitivity: 86%, specificity: 93%, accuracy: 0.87). In patients with secretory azoospermia, histopathology was again the most accurate parameter (accuracy: 0.74), especially in patients showing Sertoli cell-only pattern (accuracy: 0.83) but not in patients showing maturation arrest (accuracy: 0.55). In patients with serum FSH concentrations > 12 IU/l and maximum testicular volume < 15 ml, histopathology was not found to be accurate. Semen analysis, maximum testicular volume and serum FSH were not highly predictive in all subgroups studied. Our analysis shows that no strong predictors for successful testicular sperm recovery are available except for testicular histopathology.
Adult↗