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Biomedical subjects

R C Zimmermann

Publications and source records attributed to R C Zimmermann.

At least 19 recordsLinked to original sources
PubMed2001

Preovulatory treatment of mice with anti-VEGF receptor 2 antibody inhibits angiogenesis in corpora lutea.

Adult mammalian angiogenesis occurs predominantly in female reproductive organs: the ovary and the uterus. Angiogenesis is very active during corpus luteum formation. A key regulator of angiogenesis is vascular endothelial growth factor (VEGF), which is highly expressed during corpus luteum formation. Inhibition of VEGF activity can block the formation and function of the corpora lutea by preventing angiogenesis. The VEGF receptor 2 (VEGF-R2) mediates the angiogenic action of VEGF and is expressed during corpus luteum formation. We hypothesized that treatment with an antibody against VEGF-R2 would inhibit luteal angiogenesis by blocking VEGF/VEGF-R2 interaction. Immature mice were induced to superovulate with PMSG/hCG resulting in neovascularization in the corpora lutea, as evidenced by abundant staining for the endothelial-specific adhesion molecule PECAM. Multiple doses of a monoclonal antibody against the VEGF-R2 (DC101) were administered to immature mice. Treatment was initiated 2 days prior to the induction of superovulation with PMSG/hCG. This antibody inhibited luteal angiogenesis as evidenced by the lack of PECAM staining in the center of the corpora lutea. Multiple dose treatment with antibody initiated prior to gonadotropin administration could not dissociate the luteal inhibition from the consequences of inhibition of angiogenesis in the developing follicle. Administration of a single, preovulatory dose of anti-VEGF-R2 antibody, such that follicular angiogenesis would not be affected, also inhibited luteal development, demonstrating that luteal angiogenesis is required for corpus luteal development. We conclude that VEGF acting through VEGF-R2 has an obligatory role in luteal angiogenesis and corpus luteum formation.

Aging↗
PubMed2001

Short-term administration of antivascular endothelial growth factor antibody in the late follicular phase delays follicular development in the rhesus monkey.

Indirect evidence in the nonhuman primate and human suggests that angiogenesis and regulators of angiogenesis such as vascular endothelial growth factor (VEGF) may play an active role in cyclic folliculogenesis. Indeed, the follicle selected for maturation and ovulation possesses a denser microvascular network, and VEGF messenger ribonucleic acid and its protein have been identified in granulosa cells of the developing follicle during the mid- and late follicular phases, with a more intense signal in the mature follicle. The objective of this study was to obtain direct evidence in the nonhuman primate for an active role of VEGF in follicular growth and maturation by studying the effect of VEGF-blocking antibodies in this process. After documenting two normal ovulatory cycles, female rhesus monkeys (n = 7) received iv injections of anti-VEGF antibodies (0.5 mg) twice on successive days in the late follicular phase. Three monkeys also received nonspecific goat IgG (0.5 mg) twice on successive days in the late follicular phase. Daily measurements of estradiol, progesterone, LH, and FSH were obtained during the two control cycles, the anti-VEGF treatment and posttreatment cycles, and the IgG treatment cycle. Anti-VEGF antibody administration significantly lengthened the follicular phase in six of seven monkeys to 17.8 +/- 1.7 vs. 10.0 +/- 0.7 and 9.8 +/- 0.6 in control cycles and 10.7 +/- 0.3 days (mean +/- SE) in IgG-treated cycles. The expected late follicular phase rise in estradiol, as documented in the control cycles (day 0, 96.1 +/- 6.0; day 1, 125.5 +/- 20.0; day 2, 165.5 +/- 24.9; day 3, 183.8 +/- 11.0 pg/mL), was interrupted by anti-VEGF antibody treatment (99.3 +/- 5.0, day 0, preinjection control) to 63.3 +/- 12.2 (day 1), 48.5 +/- 8.7 (day 2), and 57.6 +/- 9.0 (day 3). Mean FSH levels were significantly increased by day 2 of anti-VEGF antibody treatment. After a variable delay, estradiol concentrations increased to reach a preovulatory peak in all anti-VEGF-treated animals, followed by ovulation, normal luteal function, and a normal posttreatment cycle. The data clearly demonstrate that short-term inhibition of angiogenesis with an anti-VEGF-blocking antibody during the later growth phase of the dominant follicle interferes with normal follicular development. Persistence of estradiol secretion and delayed resumption of its rise also suggest recovery of the follicle. We conclude that the angiogenic regulator VEGF is a crucial component in the process of follicular growth in the primate.

Animals↗
PubMed1999

The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine.

Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para-tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a biological marker of catecholamine function since its secretion is regulated by noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten healthy volunteers were administered AMPT in a double-blind placebo controlled study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM) decreased significantly as compared with promethazine (night 1 P=0.002; and night 2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82, GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in symptomatology and did not correlate with changes in 6-SM or MHPG. This study demonstrates in healthy controls that 6-SM reliably reflects presynaptic catecholamine depletion induced by AMPT without the emergence of behavioral symptoms.

Adult↗
PubMed1998

Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women.

Leptin has been called a hormone of reproduction, and seems to link fat and fertility. It has been speculated that the neurotransmitter norepinephrine (NE) (noradrenaline), possibly via the sympathetic nervous system, may represent the afferent signal which modulates leptin release from adipocytes. The purpose of this study was to produce a state of decreased sympathetic output by using the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this compound on the secretion of leptin from fat cells. Ten subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks using a randomized, double-blind, placebo-controlled, cross-over design. Blood samples for hormone measurements were obtained over 24 h (18 time points) on day 2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P < 0.05). Plasma leptin concentrations measured in the control group in women and men were similar to those reported previously in lean subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes with an increase of nocturnal concentrations by approximately 50%. Two-way analysis of variance reveals no significant difference in leptin secretion between the control and active groups in women and men. In summary, preliminary results do not support the hypothesis that NE represents the afferent signal from the central nervous system which modulates leptin release from adipocytes in the human. Further studies are needed to define the role of the sympathetic nervous system as well as NE in the regulation of leptin secretion and its involvement in obesity and reproduction.

Adult↗
PubMed1997

The addition of norethindrone acetate to leuprolide acetate for ovarian suppression has no adverse effect on ovarian stimulation.

PURPOSE: Our goal was to determine if the addition of norethindrone acetate (NETA) to leuprolide acetate (LA) has an adverse effect on controlled ovarian stimulation (COH) during in vitro fertilization (IVF). METHODS: Forty-one consecutive patients undergoing COH and IVF were divided into two groups and evaluated. Group 1 consisted of 18 patients who did not become pregnant following two cycles (one of each protocol). Group 2 consisted of 23 patients who became clinically pregnant following one cycle from either protocol. The standard protocol consisted of LA (1 mg) injected subcutaneously from the first day of menses until day 8 or when ovarian suppression was evident, at which time the dose was halved and COH was initiated. The study protocol was identical except 10 mg of NETA was given orally with LA for the first 8 days. Ovarian stimulation was similar in each protocol. RESULTS: No adverse effect on ovarian stimulation was evident on the addition of NETA to LA. No differences were noted in days of stimulation, peak estradiol (E2) level attained, peak E2-to-oocyte ratio, dosage of exogenous gonadotropins, number of aspirated oocytes, fertilization rate, or oocyte and preembryo quality. CONCLUSIONS: The addition of NETA does not attenuate COH in women undergoing IVF.

Adult↗
PubMed1996

The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion.

Prolactin (PRL) and melatonin (ML) secretion are mediated by dopamine (DA) and norepinephrine (NE), respectively. Alpha-methyl-para-tyrosine (AMPT) inhibits the production of CNS catecholamines (CA). The purpose of the study is to determine: (1) if AMPT inhibition of ML has the same gender-dependent effect as on PRL secretion; (2) if there is a post AMPT-induced NE depletion mood change in men and/or women. In a randomized, double-blind cross-over fashion, five healthy young males and five females were either given five doses of AMPT 1 g (active) or promethazine 50 mg (placebo) over a 28 h period, separated by 4-6 weeks. The PRL and ML concentrations were collected at regular intervals via an indwelling venous catheter and concurrently, two 12 h urinary 6-hydroxymelatonin sulfate (6-MS) measurements were made. Mood and anxiety states of subjects at baseline and post drug were assessed with appropriate rating scales at regular intervals. Light exposure beginning at dusk and lasting until dawn was controlled to no more than 200 lux during all phases of the study. The PRL secretion showed a significant interaction of drug x time (p = .0001) in women and a non-significant trend (p = .056) in men. No difference in PRL secretion was found between the two genders in the placebo condition, whereas the PRL secretion was significantly higher in the AMPT condition in women when compared to men (df 17,119, F = 1.9, p = .021). Total 24 h urinary 6-MS secretion highly correlated with ML secretion expressed as area under the curve (AUC) during both active and placebo experiments (r = 0.8, p < .01) and (r = 0.86, p < or = .01), respectively. The ANOVA reveals a significant interaction of drug x time for 6-SM excretion. There was no gender difference in AMPT suppression of 6-MS excretion. No mood changes were detected in men or women. We conclude that urinary 6-MS is a reliable indirect measure of the degree of AMPT-induced decrease in CNS NE activity as part of overall AMPT-induced reduction of central catecholamine activities. The pre and post AMPT-induced changes in 6-MS are not gender dependent, dissimilar to the AMPT-induced changes in PRL secretion. Therefore, 6-MS, in addition to PRL, should be measured when applying the AMPT paradigm in future research.

Adult↗
PubMed1996

Examining serotonin function: a modified technique for rapid tryptophan depletion.

Tryptophan (TRP) depletion was used to study serotonin because the ratio of TRP to large neutral amino acids (TRP/LNAA) determines the quantity of TRP that enters the brain. Because TRP is not universally available, a modified technique of TRP depletion was developed where a 1/4 strength preparation of an amino acid mixture (AAM) replaces TRP as the placebo. Seven healthy subjects could not differentiate between the preparations in this double-blind, placebo-controlled study. Urinary 6-hydroxymelatonin sulfate (6-MS) was monitored as a biochemical marker of serotonin. The TRP/LNAA ratio (GG = 0.001) and 6-MS secretion (GG = 0.024) were decreased, but placebo TRP levels (GG = 0.062) were not altered significantly. This modified technique facilitates the use of TRP depletion in clinical research.

Adult↗
PubMed1994

Noradrenergic dysregulation during discontinuation of cocaine use in addicts.

BACKGROUND: The primary objective of the study was to prospectively determine possible noradrenergic dysregulation in cocaine addicts by assessing biochemical, behavioral, and cardiovascular responses to intravenous yohimbine hydrochloride during early and late discontinuation of cocaine use. METHODS: Twelve male and two female hospitalized cocaine-dependent subjects (mean +/- SD age, 30.9 +/- 7.3 years) who were not seeking primary treatment for addiction participated voluntarily for monetary remuneration. Following an initial test dose of intranasal cocaine, 2 mg/kg, cocaine addicts received single-blind, monitored cocaine insufflation, 2 mg/kg three times each day, for 3 consecutive days. One to two days (early discontinuation) and 15 to 16 days (late discontinuation) after the last dose of cocaine, subjects received double-blind, randomized intravenous infusions of yohimbine hydrochloride, 0.4 mg/kg, or placebo. Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and plasma cortisol levels, anxiety-related symptoms on clinician- and subject-rated scales, blood pressure, and heart rate were measured throughout each test day. Ten of 14 subjects completed the entire study. RESULTS: Subjects had a significantly greater placebo-corrected MHPG response to yohimbine during early compared with late discontinuation. Subjects rated themselves significantly more nervous following yohimbine administration during early compared with late discontinuation. Seventy-one percent of subjects experienced a yohimbine-induced panic attack during early discontinuation compared with none during late discontinuation. CONCLUSIONS: The results of this study provide evidence of an underlying dysregulation in noradrenergic function and a vulnerability to panic anxiety during early discontinuation of cocaine use in addicts. Additional investigations of noradrenergic function appear warranted to further clarify derangements associated with cocaine addiction.

Administration, Intranasal↗
PubMed1994

24-hour profiles of salivary progesterone.

OBJECTIVES: To assess whether the known pulsatility of P secretion by the corpus luteum, which is detected in blood by P measurements, translates into fluctuations of saliva P concentrations, and to determine how well saliva P measurements reflect plasma P concentration. A second objective was to see whether there is a window in the luteal phase, where P secretion has reached its maximum capacity, but the amplitude is not very accentuated, which would be an ideal time to measure P. DESIGN: Twenty-one ovulatory women were randomly assigned to be studied on day 5, 7, or 8 after the luteinizing hormone surge. Blood samples were drawn every 20 minutes, and saliva samples were obtained hourly over a 24-hour period. Comparison between saliva plasma P was performed, and pulse analysis of plasma P was done. RESULTS: The percent variation of saliva P concentration over a 24-hour period was much higher when compared with the percent variation of plasma P concentration over the same time period (saliva P: 149%; plasma P: 107%). Also, the ratio of saliva to plasma P varied significantly between individuals (range: 0.0050 to 0.0148). A single plasma P concentration (8:00 A.M.) correlated better with the 24-hour mean plasma concentration than the respective single saliva value or the mean of two or three saliva samples (8:00 A.M. and 12:00 P.M.; 8:00 A.M., 12:00 P.M., and 8:00 P.M.). Plasma pulse frequency, mean pulse interval, pulse width, pulse amplitude, and 24-hour mean P level did not differ between the 3 study days. CONCLUSIONS: A single plasma P determination reflects more accurately 24-hour P secretion than repeated saliva P samples measured in the same individual. We could not identify a window in the luteal phase when P measurements are more representative of corpus luteum function.

Adult↗
PubMed1994

Sex steroids do not alter melatonin secretion in the human.

It is unclear whether sex steroids influence melatonin secretion in the human. In an attempt to find an answer to this important question 36 women within an age range of 19 to 40 years were studied within a 3-month period under the following conditions: natural menstrual cycle, ovulation induction with gonadotrophins, early pregnancy, and intake of monophasic or triphasic oral contraceptives. Except in the case of pregnancy, repeated measurements in the same individual were done because of the well-known large inter-individual variations in melatonin secretion. Melatonin concentration was measured in plasma samples obtained at 4-hourly intervals in a 24 h period and < 200 lux for all subjects studied. No consistent change in melatonin blood concentrations was demonstrated in response to the varying endogenous or exogenous concentrations of sex steroids. These observations suggest that circadian melatonin secretion is not significantly modulated by sex steroids.

Adult↗
PubMed1994

Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans.

The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Also, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT experiment (r = 0.93; P = 0.002), which indicates that AMPT does not alter the metabolism of M. These results demonstrate for the first time that AMPT significantly attenuates nocturnal M secretion. It is concluded that M is a good marker for characterizing the effectiveness of AMPT in inhibiting sympathetic NE activity.

Adult↗
PubMed1993

SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT: pharmacological characterization of brain uptake in nonhuman primates.

Single photon emission computed tomography (SPECT) studies of regional kinetic uptake and pharmacological specificity of [123I]methyl 3 beta-(4-iodophenyl) tropane-2 beta-carboxylate ([123I]beta-CIT) were performed in nonhuman primates (n = 41). In control experiments, activity was concentrated in striatum and in hypothalamic/midbrain regions. Striatal uptake increased for 140-180 min and displayed stable levels thereafter. Striatal to cerebellar activity ratios were 7.3 +/- 0.9 (mean +/- SEM) at 300 min. About 75% of striatal uptake was displaceable by injection of nonradioactive beta-CIT. Hypothalamic/midbrain activity reached maximal levels at approximately 45 min. A slow washout phase followed this peak activity. Activities in frontal, occipital, and cerebellar regions were characterized by an early peak (20-30 min), followed by rapid washout. Displacement studies demonstrated that striatal uptake was associated with dopamine (DA) transporters, as it was displaced by GBR 12909, a selective DA uptake inhibitor, but not by citalopram, a selective serotonin (5-HT) uptake inhibitor. The inverse was true in the hypothalamic/midbrain area, suggesting that the uptake in this area was associated primarily with 5-HT transporters. Maprotiline, a selective norepinephrine uptake inhibitor, did not affect [123I]beta-CIT uptake. In vivo site occupancy ED50 values of cocaine, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT), and beta-CIT were measured in the striatum with a stepwise displacement paradigm. In vivo ED50 values correlated strongly with in vitro IC50 values for binding to DA transporters. Infusion of high dose of L-DOPA (250 mumol/kg) failed to displace striatal [123I]beta-CIT binding, suggesting that the binding would not be affected by L-DOPA administration in Parkinsonian patients. However, studies performed with injection of d-amphetamine indirectly suggested that high synaptic levels of DA may compete with [123I]beta-CIT binding. These studies suggest that [123I]beta-CIT will be a useful SPECT tracer of DA and 5-HT transporters in living human brain.

Animals↗
PubMed1993

Urinary 6-hydroxymelatonin sulfate as a measure of melatonin secretion during acute tryptophan depletion.

The essential amino acid tryptophan (TRP) is the precursor for serotonin (5-HT), which is in turn an intermediary product in the synthesis of melatonin. Acute TRP depletion has recently been shown to decrease nocturnal plasma levels of melatonin in humans. Melatonin is metabolized to 6-hydroxymelatonin sulfate (6-SM), a highly stable end-product which is excreted into urine. To determine the effects of TRP bioavailability on 6-SM, 11 healthy volunteers underwent active and sham TRP depletion in a randomized, double-blind fashion. Samples of plasma free and total TRP, plasma melatonin, and urinary 6-SM were obtained before and after the depletion. Acute TRP depletion decreased free and total plasma tryptophan levels by more than 80% from baseline levels. Nocturnal 6-SM excretion was significantly decreased and highly correlated with decreases in plasma melatonin. These results suggest that nocturnal urinary 6-SM excretion is a valid measure of melatonin secretion under conditions of decreased 5-HT function. Collection of urine for 6-SM is considerably easier than nocturnal plasma sampling for melatonin. Further studies are needed to clarify the relationship between 6-SM excretion and other measures of 5-HT function in neuropsychiatric disorders.

Adult↗
PubMed1993

Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans.

Measurement of melatonin secretion throughout the night provides an index of net noradrenergic activity mediated by postsynaptic beta-adrenergic receptors in the pineal gland. Reduced melatonin secretion in some patients with depression might be related to reduced net noradrenergic function. However, a dysregulation in serotonin function has also been implicated in the pathophysiology of depression. The essential amino acid tryptophan is the precursor for both serotonin and melatonin production. To determine the effects of serotonin function on nocturnal melatonin secretion, eight healthy volunteers underwent active and sham tryptophan depletion in a randomized, double-blind fashion. Blood samples for melatonin and free and total tryptophan were obtained before and after the depletion. Acute tryptophan depletion decreased free and total plasma tryptophan levels to less than 20% of baseline levels. Melatonin secretion, expressed as area under the curve, was decreased in all eight subjects after tryptophan depletion when compared to sham depletion. These results suggest that reduced plasma tryptophan levels, and presumably brain serotonin concentrations, decrease nocturnal melatonin secretion in humans. Additional studies investigating the relationship between serotonin metabolism and pineal function in humans appear warranted.

Adult↗
PubMed1991

SPECT imaging of the benzodiazepine receptor: feasibility of in vivo potency measurements from stepwise displacement curves.

Iodine-123-labeled Ro 16-0154 is a high affinity, reversibly binding radiotracer for the benzodiazepine (BZ) receptor. Brain uptake of this radioligand was relatively stable and showed high ratios of specific-to-nonspecific uptake, with greater than 90% displaced by intravenous administration of BZ receptor agents. Repeated injections of increasing doses of each of five BZ drugs (Ro 16-0154, Ro 15-1788, clonazepam, alprazolam, and diazepam) yielded stepwise displacement curves, which were analyzed to measure the in vivo potencies of these agents. The relatively long half-life of 123I and the stable biologic uptake of the radiotracer allowed such potency estimations in just one experiment following a single injection of radioligand. The in vivo potencies of these five agents were highly correlated with their affinities for the BZ receptor determined with in vitro homogenate binding. A single crystal probe provided potency measurements virtually identical to simultaneously performed SPECT imaging studies. In conclusion, stepwise displacement by agents administered following the injection of the radioligand 123I-Ro 16-0154 provided a reliable means of measuring the in vivo potencies of BZ receptor agents. This in vivo determination may predict the clinical potency of BZ drugs than in vitro homogenate estimations, because the in vivo measure provides the summed effects of receptor affinity, plasma protein binding, penetration of the blood-brain barrier, and metabolism of the displacing agent.

Alprazolam↗
PubMed1990

Melatonin and the ovulatory luteinizing hormone surge.

A newly developed 125I-radioimmunoassay allows for the accurate determination of physiological concentrations of plasma melatonin. Melatonin secretion does not change significantly on the day before and the day of the luteinizing hormone (LH) surge when compared with the early follicular phase. In addition, it was confirmed that the beginning of the LH surge frequently occurs in the morning and is associated with low melatonin values (six of nine women). Supraphysiological melatonin concentrations did not decrease the midcycle LH secretion in four women studied.

Adult↗
PubMed1990

Follicular size and steroid secretion of dominant bovine follicles.

Twenty one estrogen-active bovine follicles obtained in the preovulatory period prior to the endogenous LH peak were superfused for 10h. Follicular diameter and superfusate estradiol (E2), testosterone (T) and progesterone (P4) were measured. A close correlation between follicle size and E2 secreted into the superfusate was found (r = 0.77; p less than 0.01). There was no correlation between superfusate T or P4 and follicular diameter. These data indicate that within certain limits the amount of E2 secreted can be predicted by follicle size in an in vitro superfusion system. As follicle size correlates closely with granulosa cell number in estrogen-active follicles, one can speculate that the rise in estrogen secretion is a reflection of an increase in granulosa cell number of the dominant bovine follicle. The application of these in vitro findings to the in vivo situation might help in the interpretation of the quality of ovarian stimulation with hMG/hCG.

Animals↗