IN a very recent article A. Cheikh Moussa studied meticulously the main passages of al-Jahiz dealing with the eunuchs in his Kitab al-Hayawan and Kitdb Mufakharat al-Jawiari wal-Ghilmnn' (later Hajawan and Jawdri). This is a welcome and timely contribution. In spite of the obvious centrality of the eunuch institution in Muslim history and civilization the subject was very much neglected (with the possible partial exception of its study regarding the Ottoman empire). Any systematic research into that subject will quickly show that its importance far surpasses all previous expectations. The passages of al-Jahiz are essential for the study of certain aspects of the eunuch phenomenon in Islam, and their thorough analysis is long overdue. Their detailed scrutiny by A. Cheikh Moussa (later M.) is certainly superior to anything written about them earlier. This does not imply the absence of certain flaws in that scrutiny, which are outside the scope of the present lines. In an addendum to the above cited article2, the same author expresses disagreement with a statement and a conclusion of mine included in the first installment of my study 3. The statement relates to the attitude towards the black eunuchs as compared to the attitude towards unemasculated blacks in major Muslim centers. The conclusion is about the term khadim in the sense of ?eunuch>> in the Muslim Medieval (especially historical and related) sources. Since he deals with the first of the two very briefly, and since I myself

The article addresses the clinical query whether a casual determination of 24-hour urinary calcium excretion by the end of first-year treatment with alendronate in osteoporotic postmenopausal women correlates with the change in bone mineral density achieved during that year. The study included 2 arms: a prospective arm (n = 31) with women on long-term hormone replacement therapy were followed for 1 year after addition of alendronate (10 mg/daily); a retrospective arm (n = 33) with women using alendronate for 1 year. Bone mineral density and urine deoxypyridinoline were measured at baseline and 1 year, 24-hour urine calcium was obtained at 1 year. All patients used supplemental calcium, but the exact intake values were not determined. The results demonstrated no correlation between the annual increase in both spine and femur bone density and urinary calcium. Assuming that urinary calcium correlates with calcium intake and absorption, a casual measurement of urinary calcium excretion seems irrelevant for the titration of optimal calcium supplementation in this clinical setup.

Sir, In the past, diabetic subjects who were showing clear signs of secondary oral drug failure would have to be treated with additional insulin. Now we have the alternative option of adding a thiazoledinedione, known for its ‘insulin sensitising’ activity, to the failing oral treatment. We assessed the effectiveness of this course in ‘real life’. Suitable patients on maximal doses of oral hypoglycaemic drugs were started on rosiglitazone treatment, in most cases 4 mg/day. A few were using added insulin. None had a history or presence of congestive heart failure (CHF), liver disease, or oedema. Treatment benefit was taken as a decrease in HbA1c of at least 0.5%. Treatment was taken to have failed if no improvement in HbA1c level was seen after three months, or the weight rose unacceptably to the physician or the patient, or a decrease in Hb or oedema was noted. Follow up in all subjects was for two years. Of the 112 patients, rosiglitazone was discontinued in 47 patients (42%) in the first year period, mostly because of lack of effect of the drug or weight gain. At entry, the HbA1c of treatment failures was not different from that of those who benefited. Weight gain was 3.36 kg. Side effects were usually apparent within two months. Oedema appeared in 8% of patients. No CHF or liver damage was seen. The HbA1c results of patients who remained on rosiglitazone were: initially 9.3%±1.2 (mean±SD; n=71); at six months 7.75±1.38 (n=71); at one year 7.8±1.06 (n=65); and after two years 7.35±1.0 (n=34). The duration of diabetes, age, BMI or initial HbA1c level did not influence the rate of success. Of the 65 patients who did benefit from the addition of rosiglitazone up to one year, 10 patients were lost to follow up during the second year; of the 55 remaining patients, 21 dropped out. Thirty-four maintained satisfactory HbA1c levels up to two years. This real-life study, which included unselected patients with secondary oral drug failure, shows initial positive effects of rosiglitazone in a majority of cases. However, the long-term, inexorable course of diabetes is already apparent when comparing results after six months and one year, at which time half of the patients start an upward trend of HbA1c levels, resulting in late drug failure; after two years only one third of patients still benefit from the drug. We could not predict drug failure or side effects; drug failure was seen amongst those patients whose HbA1c started to rise in the second half-year treatment period. Those patients who had a further improvement of HbA1c in the second half of the first year tended to remain stable or even slightly improve over the second year of follow up. Our patients received rosiglitazone as ‘a last resort’; their average initial HbA1c was high. In order to confer greater benefit rosiglitazone should be given earlier in the course of diabetes. Until now, no clinical studies on rosiglitazone in secondary oral drug failure have been published.

Objective: To examine the predictive value of bone mineral density measurements done as early as months 3 and 6 after initiation of alendronate therapy (10 mg daily) in osteoporotic women already using long-term hormone replacement therapy. Method: Lumbar spine and femoral neck bone density (DPX by Lunar) were performed at baseline, 3, 6, 12 months of combined therapy. The study group included 45 women at baseline, but 2 dropped-out at day 67 and at month 6 because of gastric complaints, leaving 43 women for analyses. Results: Group characteristics at baseline were as follows: mean age 61±5 years, mean duration of HRT use 7±3 years, lumbar spine bone density 0.863±0.089 g/cm2, with a t-score of −2.75±0.8 S.D., and femoral neck density 0.706±0.085 g/cm2 with a t-score of −2.28±0.7 S.D. Bone density increased during 1 year of combined therapy, totaling a 3.2% gain for the spine and a 2.4% gain for the femur. Most of the annual change was already observed at month 3: 2.1% for the spine and 1.4% for the femur. Moreover, the baseline to month 6 percentage difference showed a very good correlation with the yearly outcome (r=0.74, P<0.001 for both spine and femur). When different arbitrary cut-off definitions for a successful treatment (1%, 1.5% or 2% gain in density) were used in analyses, in the majority of cases the bone density at 1 year, whether elevated or not, could be predicted by months 3 and 6 results. Although urine deoxypyridinoline decreased throughout the study period, demonstrating a significant time trend (P=0.001), the baseline to month 3 changes did not correlate with baseline to annual bone density results. Conclusions: In specific clinical settings when patients or physicians are looking for a good way to anticipate whether additional alendronate in hormone users would turn out to be beneficial, bone density measurements performed as early as 3–6 months after initiation of therapy might give the answer.

AbstractAdvanced glycosylated end products (AGEs) are implicated in the pathogenesis of damaging complications seen in diabetes. They are formed by non‐enzymatic glycosylation, have cross‐linking properties with amino acids and interfere with normal functioning of vascular and other tissues. AGEs arise mostly in the hyperglycaemic milieu of diabetes. Little attention has been devoted to major extraneous sources of AGEs, such as cooked food and other more unexpected products such as cola drinks and instant coffee. Also, tobacco and tobacco smoke give rise to enhanced AGE formation. Most diabetologists and dietitians are unaware of this unwanted contribution to diabetic complications. AGEs formed in heated foods containing protein and fructose are absorbed with a bioavailability of about 10%, and their excretion is increasingly impaired as kidney function decreases. The contribution of exogenous AGEs may be greater than those formed endogenously. New avenues are being developed to reduce the burden of AGEs. Copyright © 2003 John Wiley & Sons, Ltd.

Objectives: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. Methods: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery - the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. Results: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. Conclusions: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Objectives. To compare the effect of various oestrogen and oestrogen/progestin preparations on bone density over a 2-year follow-up period in early postmenopausal women.Setting. A retrospective study on 315 women followed in a menopause clinic.Design. Antero-posterior lumbar spine bone densitometry was performed at baseline and between 18 and 24 months (mean 22 months) after initiation of hormone therapy. Participants were divided into six groups: women taking conjugated equine oestrogen (CEE) (n = 30); CEE plus sequential monthly medroxyprogesterone acetate (MPA) (n = 52); CEE plus sequential bimonthly MPA (n = 51); oral estradiol plus sequential monthly norethisterone acetate (n = 52); transdermal estradiol plus sequential monthly MPA (n = 30). A control group (n = 100) was composed of nonusers of hormones.Results. Hormone users, as a whole (n = 215), increased their bone mineral density (BMD) by 2.9% (4.8) as compared to the controls who lost 3.5% (3.4; P < 0.001). There were similar gains in BMD amongst the five study groups. Calcium supplementation was associated with better results in all women: users of hormones and calcium had a gain in BMD of 4.5% (4.8) compared to only 1.5% (4.5) in those on hormones but without calcium (P < 0.001); amongst the controls, women using calcium lost 1.4% (2.4), whilst nonusers of calcium lost 3.7% (2.4; P < 0.001.). A dose-response curve was found between basal BMD and the effect of hormone therapy: women with osteoporosis (T-score <75%) demonstrated the largest increase in BMD 6.3% (4.6), osteopenia (T-score 75-85%) was associated with a gain of 3.2% (5.6), low-borderline values (T-score 86-100%) gave a modest increase of 1.3% (4.3), and those with more than average BMD values (T-score >100%) actually lost bone despite hormone treatment [-2.1% (4.1)].Conclusions. All hormone regimens had a similar bone conserving effect. Basal BMD value may serve as a predictor for the success of treatment. Calcium supplementation should be recommended in all postmenopausal women.

Long-term hormone replacement therapy (HRT) may be considered for primary and secondary prevention of cardiovascular diseases in postmenopausal women [ 1 Sullivan J.M. Coronary arteriography in estrogen-treated postmenopausal women. Prog Cardiovasc Dis. 1995; 38: 211-222 Abstract Full Text PDF PubMed Scopus (17) Google Scholar , 2 Ettinger B. Friedman G.D. Bush T. Quesenberry Jr., C.P. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol. 1996; 87: 6-12 Crossref PubMed Scopus (317) Google Scholar , 3 Grodstein F. Stampfer M.J. Manson J.E. et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. New Engl J Med. 1996; 335: 453-461 Crossref PubMed Scopus (1285) Google Scholar ]. This cardioprotective effect has been attributed to several alterations which occur during HRT, such as changes in lipid profile, carbohydrate metabolism, hemostatic balance, endothelial function, and rate of development of coronary atherosclerosis [ 4 White M.M. Zamudio S. Stevens T. Tyler R. Lindenfeld J. Leslie K. Moore L.G. Estrogen, progesterone, and vascular reactivity: potential cellular mechanisms. Endocrine Rev. 1995; 6: 739-751 Google Scholar , 5 Mijatovic V. Pines A. Menopause-induced changes in cardiovascular functions and HRT. Eur Menopause J. 1995; 2: 4-9 Google Scholar ]. Calcium channel blocking effect was also suggested as one of the underlying pathophysiological mechanisms related to the action of estrogens [ [6] Collins P. Rosano G.M.C. Jiang C. Lindsay D. Sarrel P.M. Poole-Wilson P.A. Cardiovascular protection by oestrogen—a calcium antagonist effect?. Lancet. 1993; 341: 1264-1265 Abstract PubMed Scopus (269) Google Scholar ]. In principle, such property could be manifested by changes in heart rate and in the function of the conduction system. Herein, we report on antiarrhythmic and rate control effects of estradiol in human atrial strips.

Hypothyroidism, which is a common disorder among postmenopausal women, may be associated with higher than average bone mineral content. Contrarily, treatment with L-thyroxine may cause a significant bone loss. The aim of our study was to evaluate the effects of hormone-replacement therapy (HRT) on bone density in women with subclinical hypothyroidism treated with L-thyroxine. A total of 73 postmenopausal women with thyroid-stimulating hormone (TSH) levels > 5 mU/l and normal free thyroxine values, who never used HRT or L-thyroxine, were divided into three groups according to the treatment given during a 3-year follow-up period: 34 women received only HRT; 20 women received HRT and L-thyroxine, and the remaining 19 women received neither medications. A euthyroid control group included 41 postmenopausal women with TSH levels between 0.5 and 1.5 mU/l, who were using HRT since the initial visit. Lumbar spine bone density measurements were performed at baseline and study termination. Taken as a whole, the hypothyroid women had a non-significant higher baseline bone mineral density (BMD) as compared to the euthyroid controls (1.068 +/- 0.19 g/cm2 vs. 1.024 +/- 0.15). After 3 years, both the euthyroid and hypothyroid women on HRT only had an increase in BMD (0.032 +/- 0.04 g/cm2 and 0.028 +/- 0.05 g/cm2, respectively; p < 0.001 for both, compared to baseline). Hypothyroid women using no medication had a decrease of 0.034 +/- 0.07 g/cm2 in BMD, and those receiving both HRT and L-thyroxine lost the most: 0.04 +/- 0.08 g/cm2 (p < 0.05 for both, compared to baseline). The addition of L-thyroxine thus prevented the beneficial effect of HRT on BMD. Thyroid hormone replacement is recommended only when overt symptoms of hormone deficiency occur. In such cases, a single bone-conserving treatment with HRT may not suffice.

1. Sex hormones may influence gastrointestinal motility and thus may be responsible for symptoms that are common during pregnancy or hormone replacement therapy. The purpose of this study was to evaluate the effect of estradiol on the gut.2. Segments of rat ileum (n = 9) were suspended in an organ bath and exposed to increasing concentrations of carbachol, in the presence or absence of 17 beta-estradiol. 17 beta-estradiol markedly reduced the force developed by the ileum in response to carbachol.3. These results suggest that estradiol reduces gastrointestinal motility, (C) 1998 Elsevier Science Inc.

To evaluate the acute hemodynamic effects of 4 mg estradiol given sublingually. Design Rest and exercise echocardiographies were performed prior to estradiol administration. Then, another set of tests was done post-dose: rest examination at 1 h post-dose, isometric exercise at 65 min post-dose, and dynamic exercise at 100 min post-dose. Results The administration of 4 mg sublingual estradiol to 24 postmenopausal women (aged 48–58 years) was followed 60 min post-dose by a surge in mean estradiol serum levels (1759 ± 704 pg/ml). At rest a slight drop in systolic and diastolic blood pressure was measured after estrogen ingestion: 132 ± 24 mm Hg versus 127 ± 21 mm Hg, p < 0.05; 83 ± 11 mm Hg versus 78 ± 10 mm Hg, p < 0.02. There were no changes in resting heart rate, double product, or vascular resistance. The left heart cavities became smaller: the left atrium diameter decreased from 33.7 ± 4 mm to 32.3 ± 4 mm, p < 0.01; the end-systolic diameter decreased from 24.9 ± 3 mm to 23.6 ± 4 mm, p < 0.01; the end-diastolic diameter decreased from 44.5 ± 4 mm to 42.7 ± 4 mm, p < 0.01. The peak aortic blood flow velocity fell from 120 ± 19 cm/s to 116 ± 22 cm/s (p < 0.05), and the flow velocity integral fell from 26.3 ± 4 cm to 24.9 ± 5 cm (p < 0.01); the cardiac output underwent a small change, with borderline significance: 7 ± 2 L/min versus 6.7 ± 2 L/min, p = 0.06. Only minor changes in the hemodynamic and echocardiographic parameters were recorded after estrogen for both isometric and dynamic exercises. Analyses were also made for two subgroups: 13 normotensive women were compared with 11 hypertensive women. The post-estrogen decreases in resting blood pressure and in peak blood velocity were observed only in the hypertensive subjects, whereas the changes in heart dimensions and in flow velocity integral were the same in both subgroups. Conclusions Sublingual estradiol was associated with acute hemodynamic alterations mainly at rest but also after exercise. (Menopause 1998;5:79–85. ± 1998, The North American Menopause Society.)

We present a programmable, clinically oriented classification of pituitary adenomas (PA), based on the previous classification of Hardy and Wilson and the experience of our multidisciplinary ''Pituitary Club''. We analyzed 472 consecutive patients with PA: 292 operated transsphenoidally and 180 non operated (mainly micro and macroprolactinomas). The ''Endocrinological Classification'' is divided in: 1) Clinically functioning PA: GH, PR( for prolactin), ACTH, TSH. Mixed PA are defined by the codes GI-I-PR, GI I-TSH, etc. 2) Clinically non functioning PA: divided in NF, secreting a inconsequential glycoprotein (LH, FSH alpha subunit, beta FSH, beta LH, beta TSH) and NS, biochemically non secreting PA (silent GH, ACTH, etc.). The ''Anatomical Classification'' is based on the grade (behaviour and size of the PA: invasive, non invasive - macro, microadenoma) and the stage (supra, infra, extra and parasellar extensions of the PA).

The authors present 324 consecutive cases of sellar region pathology operated on in the last six years using a transnasal transsphenoidal extramucosal technique through one nostril approach. The approach was through the right nostril. Cutting at the base of the nostril to permit a larger access or dissection of the nasal mucosa was never performed. The septum was pushed aside together with the mucosa at the septal insertion on the sphenoid. The 324 cases included: 292 pituitary adenomas and 32 cases of other pathologies. Complications and results are comparable with the best series.In conclusion, we think that the one-nostril, extramucosal approach is simpler, quicker and safer than the classic sublabial and/or submucosal appoach.

Study Objectives: To compare the effects of four techniques for preventing or blunting the hypertensive response to the insertion of Mayfield headrest skull pins: intravenous (IV) alfentanil (ALF), esmolol (ESM), thiopental sodium (TPL), and local anesthesia using plain lidocaine (Xylocaine; XYL).Design: Randomized open study.Patients: 40 adult patients undergoing intracranial or spinal surgery requiring the use of Mayfield headrest skull pins for head positioning and immobilization.Interventions: 20 minutes after anesthetic induction, and 2 to 3 minutes prior to the insertion of headrest skull pins, one of three drugs was administered IV: ALF 10 mcg/kg, ESM 1 mg/kg, or TPL 1.5 mg/kg. The fourth drug, XYL, was administered by injection into the scalp.Measurements and Main Results: Blood pressure and heart rate (HR) were recorded immediately prior to and after pin insertion with balanced general anesthesia, and at 30, 60, 120, and 180-second intervals after pin insertion. The measurements were compared with the immediate preinsertion values. In the ALF and XYL groups, there was no significant increase in mean arterial pressure (MAP) or HR for any of the measurement periods. MAP was elevated immediately on pin insertion and for up to 2 minutes in the TPL group, and for up to 3 minutes in the ESM group (p < 0.05). HR changes were seen in the TPL group for up to one minute (p < 0.05). Increases in systolic blood pressure were seen in the TPL and ESM groups for up to 3 minutes, and in diastolic blood pressure for up to 2 minutes (p < 0.05). No other significant changes were observed.Conclusions: IV ALF and local injection of XYL in the scalp prevent the hemodynamic response to the insertion of skull pins in anesthetized patients. Neither ESM nor TPL prevented the hypertensive response. Local anesthetic injection into the scalp requires coordination between the anesthesiologist and surgeon, it carries the risk of needle stick injury, and it must be repeated if the surgeon repositions the headrest. The rapid onset and short half-life of ALF, coupled with the absence of hemodynamic effects at the dose used, makes this drug an alternative to the use of XYL injection.

A very rare case of a menstruating infertile woman with isolated luteinizing hormone (LH) hypergonadotrophinaemia is presented. There were no signs indicating the presence of a pituitary microadenoma, and LH had normal bioactivity and normal molecular weight. Likewise, no mutation was detected in the coding region of the LH beta-chain gene. In a non-stimulated cycle and a clomiphene citrate cycle, the patient developed an unruptured cyst. The patient ovulated and conceived twice following the addition of human chorionic gonadotrophin. A partial resistance at the ovarian LH receptor site, perhaps caused by a mutation, is a possible explanation for these findings. Another possibility is a malfunction in the signal transduction system of LH beyond the receptor level.

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 ± 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 ± 3 mm at baseline to 44.4 ± 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 ± 4 mm and 23.9 ± 4 mm (p = 0.006); for left atrium diameter, it was 34.5 ± 4 mm and 32.5 ± 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 ± 2 mm and 19.3 ± 2 mm (p = 0.02); for left ventricular mass, it was 197 ± 28 g and 179 ± 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 ± 18 cm/s before therapy versus 129 ± 23 cm/s while on hormone substitution (p = 0.04), and 13.6 ± 3 m/s2 versus 16.5 ± 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 ± 19 mm Hg versus 28 ± 13 mm Hg (p = 0.03) during dynamic exercise, and 43 ± 22 mm Hg versus 25 ± 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.

A novel non-competitive idiometric time-resolved fluoroimmunoassay for the determination of serum progesterone was developed, based on the use of two types of anti-idiotypic antibody that recognize different epitopes within the hypervariable region of the primary antiprogesterone antibody. The first anti-idiotype, the betatype, competes with progesterone for an epitope of the primary antiprogesterone antibody at the binding site. The second anti-idiotype, the alphatype, binds to the antiprogesterone antibody in the presence of progesterone, but does not bind to the betatype antiprogesterone complex due to epitope proximity. In the present configuration, the biotinylated alphatype was captured onto anti-biotin IgG which was immobilized on microtiter wells. Reaction mixtures containing europium-labeled antiprogesterone antibody complexed sequentially with progesterone in standards or serum samples and with the betatype anti-idiotypic antibody were then reacted with the immobilized alphatype anti-idiotypic antibody. After 30 min of incubation, the fluorescence of europium is measured by time-resolved fluorescence and is proportional to the concentration of progesterone over the range 0-320 nmol/mL. The method demonstrates good sensitivity, precision, and comparability with a direct competitive radioimmunoassay. The idiometric assay for progesterone is suitable for dipstick technology and biosensors.

OBJECTIVE:To test the hypothesis that impaired fertility in human patients with high LH concentrations throughout the follicular phase of the menstrual cycle reflects premature maturation of their oocytes.DESIGN:Previous information that resumption of meiosis is induced by lower hCG concentrations than that required for stimulation of follicular rupture was confirmed and used for establishment of a rat animal model in which oocyte maturation and ovulation can be separated experimentally. In further experiments hypophysectomized, pregnant mare serum gonadotropin (PMSG)-primed, immature female rats injected with 1.1 IU of hCG, a dose found to induce maturation in 72.9% +/- 6% of the rats with no effect on ovulation, were administered with a second injection of an ovulatory dose (4 IU) of hCG, 24 hours later. The ovulated eggs were subjected to IVF.RESULTS:Fertilization and first cleavage in oocytes recovered from our experimental animal model were similar to that observed in control PMSG-primed, either hypophysectomized or intact rats, treated by a single injection of 4 IU of hCG.CONCLUSIONS:The extension of the time interval between oocyte maturation and ovulation in the rat does not result in a lower rate of fertilization or a reduced incidence of cleavage. However, an inferior developmental capacity of these embryos cannot be ruled out.