Should high BMI be a reason for IVF treatment denial?

Our aim was to examine the influence of BMI on the live-birth rate following IVF/ICSI and evaluate its specific contribution among other factors thus enabling accurate reproductive policy development. All patients that underwent IVF/ICSI at our center during January 2012-July 2015 were included in this retrospective study. A total of 1654 ICSI cycles were divided into four groups according to the patient's BMI (kg/m2): group I (normal weight): <25 (943 cycles); group II (overweight): 25-30 (403 cycles); group III (obese): 30-35 (212 cycles); group IV (morbid obesity): >35 (96 cycles). Comparing the four groups of BMI, mean age and number of previous ART cycles was significantly lower in group I compared to groups II, III and IV. Length of treatment was significantly shorter in group I compared to groups II, III and IV. Ovarian response to COH was comparable in terms of mean estradiol and progesterone levels on the day of hCG administration mean number of oocytes retrieved, fertilized and number of embryos transferred. Endometrial thickness was significantly lower in group IV. Outcome measures, such as implantation rate, clinical pregnancy rate (CPR) per cycle and per ET, as well as live-birth rates did not differ significantly between the groups, although in group IV LBR per cycle and per ET was lower. Multivariate logistic regression stepwise analysis found a significant correlation between age and BMI but did not find correlation between BMI and clinical pregnancy (p = 0.436) or LB (p = 0.206). The results of our relatively large retrospective study did not demonstrate a significant impact of BMI on the ART cycle outcome. Therefore, BMI should not be a basis for IVF treatment denial.

An upper limit of gonadotropin dose in patients undergoing ART should be advocated.

AIM: As no upper limit of the daily dose of gonadotropins (DD GN) used for controlled ovarian hyperstimulation (COH) in patients undergoing assisted reproductive technology (ART) has been established, we aimed to evaluate the efficacy of using different DD GN in terms of live-birth achievement. METHODS: Data of patients treated at a single university medical center during the same period was analyzed retrospectively. Four groups were analyzed according to the DD GN administered: group I ("high dose"): >225- ≤ 375 IU; Group II ("Very high dose"): 376-450 IU; group III ("extremely high dose"): 451-600 IU. Normo-responders treated with DD GN ≤250 IU served as control (C). Variables included were DD GN, total GN dose/cycle, age, FSH, BMI, gravidity, parity, cycle number, IVF/ICSI, infertility diagnosis treatment protocol and outcome parameters. RESULTS: The analysis of 1394 treatment cycles of 943 patients indicated that DD and total dose of GN correlated negatively with the number of oocytes, implantation, clinical pregnancy and live-birth rate (25.9%, 14.6%, 11.4% and 4.7% in groups C, I, II and III, respectively) The logistic regression analysis indicated that the adjusted odds ratios for LBR correlated inversely with the DD administered - independently from age, baseline FSH, BMI and previous failed cycles. CONCLUSIONS: Increasing the daily dose of GN to doses higher than 450 IU or a total dose of 3000 IU/cycle is at least questionable if not harmful.

The place of selective hysterosalpingography and tubal canalization among sub-fertile patients diagnosed with proximal tubal occlusion.

OBJECTIVE: To evaluate the efficacy of selective salpingography and tubal canalization (TC) procedure among patients diagnosed with proximal tubal occlusion (PTO). METHODS: We conducted a retrospective cohort study on 61 sub-fertile patients aged 32.6 ± 4.9 years that were referred between the years of 2011 and 2013 with the diagnosis of PTO by prior hysterosalpingography. Patients underwent TC and were classified as bilateral PTO or unilateral PTO. Information regarding the patient's reproductive outcome within the 12 months following the procedure was collected by a telephone survey. RESULTS: During the study period, 58/61 (95 %) patients underwent TC, resulting in bilateral open tubes in 54 patients (93.1 %). 53/58 (91.3 %) patients answered our survey. There were 23/53 (43.4 %) patients with a successful procedure who conceived after spontaneous or COH + IUI resulting in 15/23 live births (65.2 %). CONCLUSION: Tubal canalization is a safe and minimally invasive procedure that can be used effectively to restore patency in a proportion of cases of PTO thus avoiding the need for expensive and invasive procedures such as assisted reproductive techniques.

High rates of abnormalities in hysterosalpingography in couples with male factor infertility.

The rate of anatomical abnormalities in infertile couples with obvious male factor is unknown. For this purpose the authors retrospectively analyzed 376 hysterosalpingographies (HSG) of couples with severe male factor. Patients were subdivided into four groups according to the woman's age, and primary or secondary infertility: A--less than 35-years-old, primary infertility, B--less than 35-years-old, secondary infertility, C--35-years-old or more, primary infertility, and D--35-years-old or more, secondary infertility. Overall, abnormalities in HSG were demonstrated in 25.5% of the patients, and in 18, 21, 52, and 40 percent of patients in groups A, B, C and D, respectively. Age was found to be a significant independent risk factor (p < 0.05) while primary or secondary infertility was not. The adjusted odds ratio for woman who were 35-years-old or more to have any abnormalities in HSG were 3.7-fold greater (95% CI 2.2- 6.23), than women who were less than 35-years-old. In conclusion, relatively high rates of female mechanical abnormalities may be found even in infertile couples with obvious male factor and are significantly more prevalent in older women.

Effect of seminal plasma application to the vaginal vault in in vitro fertilization or intracytoplasmic sperm injection treatment cycles-a double-blind, placebo-controlled, randomized study.

PURPOSE: To study whether intravaginal application of seminal plasma after follicle aspiration has the potential to increase implantation and clinical pregnancy rates after IVF-ET. METHODS: We conducted a prospective, double-blind, placebo-controlled randomized study of 230 patients undergoing IVF-ET cycles. 500 µL of Fresh seminal plasma from the patient's partner or culture medium (placebo) were injected in the vaginal vault just after follicle aspiration. The main outcome measured was ongoing clinical-pregnancy rate. RESULTS: After ET cancellation in ten patients due to lack of fertilization or embryo cleavage, 220 embryo transfers (103 and 117 in the study and control groups) resulted in a clinical pregnancy rate of 36.9 % and 29.1 % for the study and control groups, corresponding to a relative increase of 26.8 %. After an early pregnancy loss of 13.1 % (5/38) and 23.5 % (8/34) in the study and control groups respectively an ongoing pregnancy rate of 32.0 % (33/103) and 22.2 % (26/117) was achieved corresponding to a relative increase of 44.1 %. Multivariate logistic regression analysis adjusted for study group, age, infertility, and cycle characteristics did not demonstrate any parameter that could predict occurrence of clinical pregnancy rates after IVF-ET. CONCLUSIONS: Patients who underwent SP intravaginal insemination after oocyte pick-up reached higher implantation and clinical pregnancy rates following ET compared to controls, although the difference did not reach statistical significance. More studies and variable methodologies may clarify the potential clinical effect of SP in improving live birth rates after ART.

Presence of IL-18 in testicular tissue of fertile and infertile men.

Recently, IL-18 was identified in human testes. Moreover, an inverse correlation was found between the levels of IL-18 and the number and motility of spermatozoa. We examined the presence of IL-18 protein in normal and impaired spermatogenesis. Testicular tissue specimens were taken from 25 nonobstructive azoospermic patients undergoing testicular sperm extraction and from autopsies of three healthy controls. The presence of IL-18 in human testicular cells was examined by immunohistochemical staining of paraffin-embedded sections, using a specific antibody for human IL-18. In testicular tissue of healthy controls as well as in study cases, presence of IL-18 was identified in somatic, mitotic, meiotic and post-meiotic cells in correlation with their presence. In all patients, Leydig cells were less intensively stained. Mitotic cells were immunostained in the control group and less intensively in hypospermatogenesis and maturation arrest subgroups. Primary spermatocytes were in general most efficiently stained. The expression of IL-18 mRNA (as examined by real-time PCR analysis) showed significantly lower expression in testicular tissues with impaired spermatogenesis when compared to normal tissues. We report the first study demonstrating the presence of IL-18 in human testicular tissue at the protein level. The presence of this cytokine in somatic as well as in different types of germ cells may suggest its involvement in the regulation of the spermatogenic process and steroidogenesis under physiological and pathological conditions.

Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome.

BACKGROUND: The genital malformations in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy. METHODS: The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome. RESULTS: The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 ± 1297IU for 13 ± 2.3 days versus 2975 ± 967 IU for 11.6 ± 1.6 days, P≤ 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 ± 6 versus 8.9 ± 5.4, P≤ 0.03, metaphase II (MII) oocytes 8.7 ± 5.1 versus 6.7 ± 4.8, P≤ 0.05, fertilizations 6 ± 3.6 versus 4.4 ± 3.3, P≤ 0.03 and cleaving embryos 5.7 ± 3.8 versus 4.1 ± 3.3, P≤ 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups. CONCLUSIONS: Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes, fertilizations and cleaving embryos was higher among women with the typical form. Pregnancy rates were similar since the available number and quality of transferred embryos to the surrogate mother were not affected.

The possible association between IVF and breast cancer incidence.

BACKGROUND: The possible association between ovulation-inducing drugs and breast cancer development has been debated. Our aim was to evaluate the incidence of breast cancer in a cohort of women exposed to in vitro fertilization (IVF). METHODS: A retrospective cohort analysis was performed by linkage of the computerized database of all women treated at the IVF Unit at Assaf Harofeh Medical Center between 1986 and 2003, and the Israeli National Cancer Registry. The standardized incidence ratio (SIR) was computed as the ratio between the observed number of breast cancer cases and the expected cases, adjusted for age and continent of birth, in the general population. Tumor characteristics of the IVF patients were studied by reviewing original medical records. RESULTS: 35 breast carcinomas were diagnosed among 3,375 IVF-treated women, compared to 24.8 cases expected (SIR = 1.4; 95% CI 0.98-1.96). Age >or=40 years at IVF treatment (SIR = 1.9; 95% CI 0.97-3.30), hormonal infertility (SIR = 3.1; 95% CI 0.99-7.22), and >or=4 IVF cycles (SIR = 2.0; 95% CI 1.15-3.27) were found to be risk factors to develop breast cancer compared to the general population. Multivariate analysis revealed that women who underwent >or=4 IVF cycles compared to those with one to three cycles were at risk to develop breast cancer, although not significantly (SIR = 1.9; 95% CI 0.95-3.81). Of IVF-treated women 85% had ER(+) tumors and 29% had positive family history. CONCLUSIONS: A possible association between IVF therapy and breast cancer development was demonstrated, especially in women >or=40 years of age. These preliminary findings need to be replicated in other cohort studies.

Morphology assessment and fluorescence in situ hybridization of the same spermatozoon using a computerized cell-scanning system.

BACKGROUND: Poor sperm morphology is statistically associated with an increase in the incidence of chromosome abnormalities. Our aim was to examine the possible correlation between chromosomal aberrations and sperm morphology in the same cell. METHODS: 12349 spermatozoa from 7 teratozoospermic and one globozoospermic patients, and from 3 fertile donors were analyzed using a system which scans for cell morphology and chromosomal ploidy in the same cell using digital technology. RESULTS: Chromosomal aberrations were detected in 5.3% of teratozoospermic cases and in 6.7% in the globozoospermic patient compared with 1.6% in donors (P < 0.0001). Chromosomal aberrations were more common in abnormally formed sperm compared with normal spermatozoa: 4.5% vs 1.3% in the teratozoospermic group and 2.0% vs 0.3% in the control group (NS), especially frequent among sperm with two heads or two tails (52.1-77.2%) or extreme head deformations (10.6-11.1%) irrespective of grouping, and in mild amorphous heads in the globozoospermic patients (20.2%). The frequency of chromosomal aberrations in morphologically normal sperm was comparable whether derived from teratozoospermic or normospermic patients. CONCLUSIONS: The computerized cell-scanning system demonstrated the relationship between chromosomal aberrations and sperm morphology in the same spermatozoon. The incidence of chromosomal aberrations was positively linked to abnormal sperm morphology, the more severe the abnormality, the higher the incidence of aneuploidy.

PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation.

LH and prostaglandin E(2) (PGE(2)) share many similar effects on the pre-ovulatory follicle. They can induce independently cumulus expansion, the resumption of meiosis and progesterone production. However, cyclooxygenase-2 (COX-2) inhibitors were found to hinder most of the LH-induced effects. Recently, EGF-like growth factors amphiregulin (Ar) and epiregulin (Ep) were found to be produced in response to LH stimulation and to induce cumulus expansion and oocyte maturation. We aimed at evaluating whether PGE(2) induces Ar and Ep syntheses in human granulosa cells and whether the inhibition of PGE(2) production by selective COX-2 inhibitor, nimesulide, affects LH-induced Ar and Ep biosynthesis. Ar and Ep mRNA levels increased following PGE(2) stimulation, in a dose- and time-dependent manner, which resembled those of LH. The blockade of protein kinase A (PKA) (by H89) and mitogen-activated protein kinase (MAPK) (by UO126) reduced the expression of PGE(2)-induced Ar and Ep biosynthesis. Although the stimulation of the cells with LH in the presence of nimesulide did not change the progesterone levels, it resulted in a significant reduction of Ar and Ep biosynthesis. In conclusion, PGE(2) may mimic LH action, at least in part, by the induction of Ar and Ep biosynthesis, which involves cAMP/PKA and MAPK pathways. The negative effect of nimesulide on the ovulatory process may be due to the reduction of Ar and Ep biosynthesis, which implies a possible collaborative role between PGE(2) and LH on their induction.

Meiotic arrest in vitro by phosphodiesterase 3-inhibitor enhances maturation capacity of human oocytes and allows subsequent embryonic development.

Controlling nuclear maturation during oocyte culture might improve nuclear-cytoplasmic maturation synchrony. We aimed to evaluate the quality of in vitro-matured, germinal vesicle (GV)-stage human oocytes following a prematuration culture (PMC) with a meiotic arrester, phosphodiesterase 3-inhibitor (PDE3-I). Follicles (diameter, 6-12 mm) were retrieved 34-36 h post-hCG administration from informed, consenting patients who had undergone controlled ovarian stimulation. Cumulus-enclosed oocytes (CEOs) presenting moderate expansion or full compaction were placed in PMC with the PDE3-I, Org9935, for 24 or 48 h. Subsequently, oocytes were removed from PMC, denuded of cumulus cells, matured in vitro, and fertilized, and the resulting embryos were cultured. In the presence of PDE3-I, approximately 98% of the oocytes were arrested at the GV stage. Following PDE3-I removal, oocytes acquired a higher maturation rate than oocytes that were immediately denuded of cumulus cells after retrieval and in vitro matured (67% vs. 46%, P = 0.01). In controls, immature CEOs retrieved with moderate expansion reached higher maturation rates compared to fully compacted CEOs, but in PMC groups, high values of maturation were achieved for both morphological classes of CEOs. No effect of PMC on fertilization was observed. A 24-h PMC period proved to be the most effective in preserving embryonic integrity. Similar proportions of nuclear abnormalities were observed in embryos of all in vitro groups. In summary, PMC with the specific PDE3-I had a beneficial effect on human CEOs by enhancing maturation, benefiting mainly the fully compacted CEOs. This resulted in an increased yield of mature oocytes available for insemination without compromising embryonic development. These results suggest that applying an inhibitor to control the rate of nuclear maturity by regulating intraoocyte PDE3 activity may allow the synchronization of nuclear and ooplasmic maturation.

The outcome of ICSI of immature MI oocytes and rescued in vitro matured MII oocytes.

BACKGROUND: The use of immature oocytes is limited to cases where these are the only available oocytes, and they are usually only microinjected with sperm after having undergone maturation in vitro. This study compares the outcome of injection of sperm into metaphase I oocytes immediately after their denudation (MI) performed 2 h after their retrieval, with the outcome of injection of sperm into rescued in vitro matured metaphase II (IVM MII) oocytes after their short incubation in routine laboratory conditions. METHODS: ICSI was performed on MI oocytes, rescued IVM MII oocytes and on MI oocytes that were incubated but failed to extrude their first polar body (arrested IVM MI). Fertilization and cleavage rates were compared with those achieved in mature metaphase II oocytes (MII). RESULTS: ICSI of MI oocytes showed impaired performance compared with ICSI of rescued IVM MII oocytes and MII oocytes, in terms of oocyte degeneration rate (11 versus 6 versus 4%; P < 0.0001), fertilization rate (28 versus 44 versus 68%; P < 0.0001) and multipronucleated fertilization (10 versus 4 versus 4%; P < 0.01). The cleavage rate was lower in rescued IVM MII oocytes compared with MII oocytes (86 versus 95%; P < 0.01). Arrested IVM MI oocytes showed similar results to those of MI oocytes but had a lower cleavage rate (72 versus 96%; P < 0.01). CONCLUSIONS: The injection of rescued IVM MII oocytes is preferred to the injection of MI oocytes.

Coasting-what is the best formula?

Coasting is a method to decrease the incidence of ovarian hyperstimulation syndrome (OHSS), which involves withdrawing exogenous gonadotrophins until the serum estradiol (E(2)) level decreases. The application of this strategy, as it appears in the literature, has been variable, with heterogeneous criteria for initiating and ending the coasting process and as a result, reports of efficacy are inconsistent. In attempt to establish a recommended protocol for coasting we reviewed and analysed 10 relevant studies, found by a Medline search. Based on the data collected, coasting should be initiated when the serum E(2) concentration exceeds 3000 pg/ml, but not unless the leading follicles reach a diameter of 15-18 mm. Its duration should be limited to <4 days, thus, preventing the decrease in implantation and pregnancy rates that occur after longer periods of coasting. Administration of hCG should be withheld until serum E(2) falls below 3000 pg/ml. Based on the published data, these suggested guidelines result in an acceptably low incidence of severe OHSS (<2%) and provide satisfactory fertilization and pregnancy rates (55-71% and 36.5-63% respectively). A multicentre randomized prospective study would help to confirm the effectiveness of this approach.

Factors influencing the outcome of ICSI in patients with obstructive and non-obstructive azoospermia: a comparative study.

BACKGROUND: Factors influencing success of sperm retrieval in azoospermic patients and outcome of ICSI were evaluated. METHODS AND RESULTS: Uni- and multifactorial analysis were performed using logistic and stepwise analysis, following surgical sperm retrieval by percutaneous epididymal sperm aspiration (55 cycles) or testicular sperm extraction (142 cycles) in 52 and 123 patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) respectively. ICSI cycles using fresh or cryopreserved-thawed sperm were included. Sperm were retrieved to allow ICSI in 100 and 41% of OA and NOA patients, with no significant correlation with patients' age or FSH level. Occurrence of pregnancy was significantly correlated with female age (90th quantile: 38 years), number of oocytes retrieved (10th quantile: five oocytes) and number of oocytes injected (10th quantile: four oocytes). Sperm origin (epididymal versus testicular), status (fresh or thawed), male partner's age, and serum FSH had no significant effect upon implantation rate, pregnancy rate per embryo transfer or spontaneous miscarriage rate. CONCLUSIONS: In OA patients ICSI should be planned in conjunction with surgical sperm retrieval. In contrast, the lack of efficient non-invasive parameters to predict sperm retrieval in NOA suggests that elective surgical sperm retrieval may be offered to these patients prior to ovarian stimulation of their partners, especially when donor back-up is not an alternative. Female factors such as age and ovarian reserve have significant impact upon clinical success rates.

Outcome of first and repeated testicular sperm extraction and ICSI in patients with non-obstructive azoospermia.

BACKGROUND: It is unclear whether or not testicular sperm extraction (TESE) should be repeated for patients in whom no sperm were found during their first TESE attempt. METHODS AND RESULTS: The outcome of repeated TESE was evaluated in patients with non-obstructive azoospermia (NOA) after failing to obtain sperm in their first extraction attempt, or having used all available cryopreserved testicular tissue. Out of 83 patients with NOA, patients repeated TESE two (n = 22), three (n = 8), four (n = 6) and five (n = 3) times. Distribution of main testicular histology included germ cell aplasia (55%), maturation arrest (29%) and germ cell hypoplasia (16%). The first TESE yielded mature sperm for ICSI in 39% of patients (sp+), and failed in the remaining 61% (sp-). A second TESE yielded mature sperm in 1/4 from the sp- group and in 16/18 from the sp+ group. At the third, fourth and fifth trials, 8/8, 5/6 and 3/3 of the original sp+ patients were sp+ again respectively. Compared with the outcome of the first trial, all further trials did not differ statistically in the rate of fertilization (54 versus 49%), implantation (9.5 versus 5.4%), or clinical pregnancy/cycle (19 versus 15%). No pregnancies were achieved among the three patients after their fifth TESE. Pregnancies occurred in all histological groups, except maturation arrest. CONCLUSIONS: The outcome of repeated TESE cycles, up to the fourth trial, justifies the procedure.

Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter's syndrome.

BACKGROUND: Recently, intracytoplasmic sperm injection (ICSI) of testicular spermatozoa retrieved surgically from patients with non-mosaic Klinefelter's syndrome resulted in several deliveries. The aim of this study was to evaluate the outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in these patients. METHODS AND RESULTS: Following informed consent regarding the genetic risks of their potential offspring, mature testicular spermatozoa were found in five out of 12 (42%) patients who underwent testicular sperm extraction, and ICSI was performed while excess tissue was cryopreserved. The mean age of the patients was 28.7 +/- 3.6 (range 23-36 years). Their baseline FSH was elevated (mean 38.3 +/- 11.4; range 22-58 mIU/ml). All patients had small testicles of 2-4 ml in volume. The outcome of ICSI using fresh or cryopreserved-thawed testicular spermatozoa during five cycles in each group, was compared. No statistical significant difference was found in the two pronuclear fertilization rate (66 versus 58%), embryo cleavage rate (98 versus 90%) and embryo implantation rate (33.3 versus 21.4%) for fresh or cryopreserved sperm accordingly. The clinical outcome after using fresh testicular sperm included two singleton pregnancies (one delivered and one ongoing) and a triplet pregnancy resulting in a twin delivery (after reduction of an 47,XXY embryo). After using cryopreserved-thawed testicular spermatozoa, two pregnancies were obtained resulting in one delivery of twins and one early spontaneous abortion. CONCLUSIONS: Outcome of ICSI using cryopreserved-thawed testicular spermatozoa of patients with non-mosaic Klinefelter's syndrome is comparable with that following the use of fresh spermatozoa. The genetic implications for the future offspring should be explained to the patients.

Influence of a short or long abstinence period on semen parameters in the ejaculate of patients with nonobstructive azoospermia.

OBJECTIVE: To compare the effect of a short (4 days) or a long (14 days) abstinence period on sperm retrieval by extended sperm preparation in patients with nonobstructive azoospermia scheduled for testicular biopsy and intracytoplasmic sperm injection (ICSI). DESIGN: A prospective case control study. SETTING: Male infertility clinic in a university hospital. PATIENT(S): Fifty male patients with nonobstructive azoospermia, scheduled for testicular biopsy for ICSI. INTERVENTION(S): Diagnosis of nonobstructive azoospermia and a thorough microscopic search for sperm cells (extended sperm preparation). MAIN OUTCOME MEASURE(S): The number of sperm cells collected, sperm motility, and total motile sperm count after short and long abstinence periods. RESULT(S): There was a significant difference between long and short abstinence with an increase in sperm count (log-to-log transformed analysis of variance P<.025) and total motile sperm (P<.025 analysis of variance, P<.02 paired Student's t-test) in the former group, but no significant change in sperm motility (Wilcoxon and paired Student's t-test). In 18 patients, sperm concentration and sperm motility were similar in a second collection, done after the same abstinence period, compared with the same parameters in the first sample. When at least 10 motile sperm were defined as the cutoff number, allowing ICSI without testicular biopsy, no significant differences were found between the two abstinence periods. No clinical or laboratory male characteristic could predict the detection of 10 motile sperm by extended sperm preparation either after a short or a long abstinence period. CONCLUSION(S): Sperm count and total motile sperm were increased after a long abstinence period, with no change in sperm motility. No additional advantages were conferred by long abstinence as opposed to short abstinence when 10 motile sperm were defined as the cutoff number for ICSI. The recommended period of abstinence for extended sperm preparation and ICSI, whether short or long, should be individualized for each patient.

Improvement of IVF outcome in poor responders by discontinuation of GnRH analogue during the gonadotropin stimulation phase--a function of improved embryo quality.

PURPOSE: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response. METHODS: Prospective case-control evaluation compared with same patient's previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing midluteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control. RESULTS: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies. CONCLUSION: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.

A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles.

The effect of 100 and 200 IU per day recombinant FSH (rFSH) on numbers of oocytes retrieved and the total dose used in ovarian stimulation before intracytoplasmic sperm injection was investigated in a double-blind, randomized multicentre trial. A total of 91 women was treated with a low-dose protocol and 88 with a high-dose regimen at five centres. For each started cycle, significantly more oocytes were retrieved in the 200 IU group than in 100 IU group (12.0 versus 5.7, P < 0.001); total rFSH consumption was 1121 and 1875 IU in the low- and high-dose groups respectively. Significant variations were noted between centres with regard to numbers of oocytes collected per started cycle, ranging from 2.8 to 7.2 in the 100 IU group and from 9.0 to 19.1 in the high-dose group. Exploratory analyses of secondary outcomes suggested there were no differences in vital pregnancy rates per started cycle (19.2 versus 16.9%) and per embryo transfer (26.2 versus 19.3%) in the low- and high dose groups respectively. There were four hospitalizations due to ovarian hyperstimulation syndrome, all in the 200 IU group.

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation.

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.