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Treatment of chronic anovulation resistant to clomiphene citrate (CC) by using oral contraceptive ovarian suppression followed by repeat CC treatment.

OBJECTIVE: To evaluate the effectiveness of a 2-month oral contraceptive (OC) ovarian suppression followed by clomiphene citrate (CC) in patients who had failed to ovulate on maximum doses of CC alone. DESIGN: Prospective, nonrandomized observational study. SETTING: Private tertiary infertility center. PATIENT(S): Thirty-eight patients with documented anovulation by transvaginal ultrasound follicular monitoring while receiving CC in doses of 150 mg or higher. INTERVENTION(S): Two-month ovarian-hypothalamic-pituitary axis suppression with OCs followed by repeat CC 100 mg for 5 days. MAIN OUTCOME MEASURE(S): Follicle growth, endometrial development, and ovulation were confirmed by transvaginal ultrasound. Pregnancy was confirmed by serum hCG levels and 7-week gestation ultrasound. RESULT(S): Thirty-eight patients completed 95 treatment cycles. Twenty-nine patients became ovulatory (76%), and 69 of the 95 cycles were ovulatory (72.6%), resulting in 22 pregnancies in the 38 patients for a cumulative pregnancy rate of 58%. CONCLUSION(S): Suppression of the hypothalamic-pituitary-ovarian axis for 2 months with OCs followed by CC treatment results in excellent rates of ovulation and pregnancy in women who had previously failed to ovulate on CC alone. This treatment offers an effective, reasonable, inexpensive, and low-risk alternative before gonadotropin therapy.

Adult↗

Urinary follicle-stimulating hormone (FSH) versus recombinant FSH in clomiphene citrate-resistant, normogonadotropic,chronic anovulation: a prospective randomized study.

OBJECTIVE: To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation. DESIGN: Prospective, randomized trial. SETTING: University-based infertility clinic. PATIENT(S): Fifty-one women. INTERVENTION(S): Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken. MAIN OUTCOME MEASURE(S): Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate. RESULT(S): Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered. CONCLUSION(S): Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol.

Adult↗

Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study.

OBJECTIVE: To compare the effectiveness of clomiphene citrate used alone and in combination with ethinyl E2 for the induction of ovulation in patients undergoing IUI. DESIGN: Randomized, double-blind study. SETTING: Four infertility treatment centers. PATIENT(S): Women aged 25-35 years with infertility of at least 2 years' duration and oligomenorrhea or amenorrhea associated with a positive menstrual response to an IM progesterone challenge. INTERVENTION(S): A total of 64 patients were randomized to treatment with CC (100 mg daily for 5 days) or CC (100 mg daily for 5 days) plus ethinyl E2 (0.05 mg daily for 5 days). MAIN OUTCOME MEASURE(S): The uterine artery pulsatility index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. RESULT(S): Both treatment regimens increased FSH, LH, and 17beta-E2 levels, with no statistically significant differences. There was a statistically significant difference in endometrial thickness between the two treatment groups. No statistically significant differences were noted in pulsatility index values or in the number of preovulatory follicles. CONCLUSION(S): Ethinyl E2 can reverse the deleterious effects of CC on endometrial thickness, which may contribute to higher pregnancy rates.

Adult↗

Growth hormone response to clonidine in anovulatory infertile women resistant to clomiphene citrate stimulation.

OBJECTIVE: To evaluate the GH response to the clonidine test in a group of infertile women and to determine their ovulatory response to clomiphene citrate (CC) stimulation. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit. PATIENT(S): Thirty-three anovulatory infertile women (age range, 25-36 years) and 9 healthy controls with normal ovulation. INTERVENTION(S): In the early follicular phase, 0.3 mg of clonidine was administered between 8:30 and 9:00 A.M. and blood samples were collected for 120 minutes thereafter for measurement of serum GH levels. Plasma levels of insulin and glucose were measured after a 75-g glucose load, and CC was given at a dosage of 50-250 mg/d for ovulation-induction. MAIN OUTCOME MEASURE(S): Serum concentrations of GH, insulin-like growth factor I, insulin, and insulin-like growth factor binding protein-1. RESULT(S): On the basis of their ovulatory response to CC, 15 patients were considered nonresponsive (group 1) and 18 patients were considered responsive (group 2). Baseline levels of GH, insulin-like growth factor I, and insulin-like growth factor binding protein-1 were similar in the two groups of patients and the controls. The GH response to clonidine was significantly greater in group 2 and in the controls than in group 1. Concentrations of insulin and glucose after the glucose load were not different among the three groups. CONCLUSION(S): Women who were resistant to CC had a reduced GH response to clonidine. These data suggest that adequate GH secretory capacity is important for CC action.

Adult↗

A randomized prospective study comparing pregnancy rates after clomiphene citrate and human menopausal gonadotropin before intrauterine insemination.

OBJECTIVE: To determine whether hMG offers an advantage over clomiphene citrate (CC) in achieving pregnancy after IUI with husband's sperm. DESIGN: Randomized prospective trial. SETTING: Infertility patients in a university teaching hospital. PATIENT(S): Fifty-eight women under 39 years old undergoing ovulation induction before IUI. INTERVENTION(S): The women were assigned randomly to one of two treatment groups. Patients in group I (CCHH) received CC for the first two cycles and hMG for the last two cycles. Patients in group II (HHCC) received hMG for the first two cycles and CC for the last two cycles. MAIN OUTCOME MEASURE(S): Cycle fecundity rates for the two treatment modalities were compared statistically with use of life-table analysis. RESULT(S): Of the 174 cycles studied, overall cycle fecundity rate was 11.11 (9 of 81 cycles) in the CCHH group and 10.75 (10 of 93 cycles) in the HHCC group. The difference was not statistically significant. The cycle fecundity rate was 14.44% (13 of 90 cycles) for cycles with CC and 7.14% (6 of 84) with hMG. The difference was not statistically significant. CONCLUSION(S): These data suggest that CC is an effective alternative to hMG in the population examined.

Abortion, Spontaneous↗

Minimal stimulation IVF using clomiphene citrate and oral contraceptive pill pretreatment for LH suppression.

OBJECTIVE: To determine if oral contraceptive pill (OC) pre-treatment prior to minimal stimulation IVF using clomiphene citrate (CC) would make the procedure easier to perform by preventing the LH surge and result in pregnancy rates (PRs) comparable to stimulated IVF. DESIGN: Prospective cohort study. SETTING: Private tertiary infertility center. PATIENT(S): Thirty-two women with tubal or pelvic adhesive disease as the cause of their infertility, ovulatory cycles, under the age of 40, and no male factor. INTERVENTION(S): Two-month ovarian-hypothalamic-pituitary axis suppression with OC followed by CC 100 mg on day 3 of the cycle for 8 days, hCG administration midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocytes retrieved, serum LH and estradiol levels, maturity of oocytes, fertilization rates, embryo number and quality, and PRs. RESULT(S): Thirty-six patients completed 71 stimulation cycles and 64 follicle aspirations. No LH surges occurred with a mean mature oocytes retrieved of 3.2, 90% fertilization rate, and mean 2.5 embryos transferred. Twenty-one of the 64 cycles resulted in a clinical pregnancy (32.8% PR per retrieval) with 2 other biochemical pregnancies and 3 twin gestations. This was not significantly different from the matched cohort stimulated IVF. CONCLUSION(S): Minimal stimulation IVF is a simple, low-cost, and low-risk alternative to stimulated IVF with comparable PRs.

Adult↗

Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin.

OBJECTIVES: To evaluate the clinical features, endocrine and metabolic profiles in clomiphene (CC) responders and non-responders with polycystic ovarian disease (PCOD), and to examine the effects of metformin (MTF) on the above parameters of CC resistance. METHODS: A prospective clinical trial was undertaken at the infertility division of a university teaching hospital. Forty-one CC responders were selected and their hormonal and clinical features were determined. Forty-one CC-resistant PCOD women were also selected and clinical features; metabolic and hormonal profiles before and after treatment with MTF 1500 mg/day for 6-8 weeks were evaluated. Women who failed to conceive were treated by CC while continuing to take MTF. RESULTS: CC responders had higher insulin levels while non-responders were hyperinsulinemic. Menstrual irregularities improved in 30%. Mean+/-S.D. area under curve of insulin decreased from 297.58+/-191.33 to 206+/-0.1 mIU/ml per min (P=0.005). Only 39.39% ovulated and 24.24% conceived. CONCLUSION: PCOD is associated with insulin resistance (IR) particularly in CC-resistant women. Insulin resistance and androgen levels are significantly higher in obese patients. MTF therapy improved hyperandrogenemia, IR, and pregnancy rate.

Adult↗

Effect of clomiphene citrate on endometrium thickness and echogenic patterns.

OBJECTIVE: To study the effect of clomiphene citrate (CC) on the thickness and echogenic pattern of the endometrium using vaginal sonography. METHOD: In this experimental prospective study, CC was given to 31 women with unexplained infertility. Thickness and echo patterns of the endometrium, as well as estradiol (E2) and progesterone (P) levels, were compared in women taking CC and in control patients during both the late proliferative and midsecretory phases of the menstrual cycle. RESULTS: Endometrial thickness was significantly thinner in women taking CC (P<0.03) than in controls during the late proliferative phase but there was no significant difference during the midsecretory phase. The endometrial echogenic patterns of women taking CC who had conceived revealed endometrial thicknesses of grade III and grade IV on midsecretory days, but these findings were not significantly different from those of women who had not conceived (P=0.3). Serum E2 level was higher in women taking CC than in the controls on both late proliferative and midsecretory days (P<0.05). CONCLUSION: CC affects endometrium thickness on late proliferative days but not on midsecretory days, and does not alter the echogenic pattern of the endometrium.

Adult↗

Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection.

The objective of this study is to evaluate the performance of clomiphene citrate (CC) challenge test to predict diminished ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI). The 198 women who underwent the CC challenge test fulfilled the following criteria; over 35 years of age, removal of one ovary or previous ovarian surgery, the presence of ovarian endometrioma or previous poor response to ovarian hyperstimulation. Of the patients tested, 141 were found to have a normal CC challenge test while 57 had an abnormal result. The cancellation rate of the cycle with a poor response was significantly higher in women with an abnormal test (36.8%) than in those with a normal test (19.8%) (P < 0.05). The sensitivity of CC test for cycle cancellation was found to be 43% with a specificity of 76%, positive and negative predictive values of 37 and 80%, respectively. The estradiol values on hCG day, the number of retrieved oocytes and metaphase II oocytes and the rate of transfer cycles were significantly lower in females with an abnormal test. Women with normal test results had higher pregnancy rates per embryo transfer than those with abnormal test results (21.5 vs. 13.3%) and the predictive value of an abnormal test for failing to conceive was 93% (53/57) with a sensitivity of 31%, specificity of 84% and negative predictive value of 15.6%. Of 57 women with an abnormal test result, 25 (43.8%) were abnormal due only to an elevated day 10 or 11 value of FSH, which could not be detected using only basal FSH screening. In this group, the cancellation rate (48 vs. 19.8%, P < 0.01), the rate of transfer cycles (48 vs. 72.3%, P < 0.05) and the mean number of retrieved oocytes (4.9 +/- 2.5 vs. 6.4 +/- 3.1, P < 0.01) were all significantly different from normal test group. Although the rate of pregnancies per started cycle (8 vs. 15.6%) did not show a statistically significant difference, this is most probably due to the low number of patients. In conclusion, an abnormal CC challenge test is a good predictor of diminished ovarian reserve and it is better than a basal FSH concentration on day 3. It provides valuable information for both patients as to their chances of achieving a pregnancy and also for the medical team deciding on options for stimulation protocols.

Adult↗

Clomiphene-induced LH surges and cetrorelix.

The following rat pituitary cell culture experiments were carried out to find an explanation for the increased premature LH surges in stimulation protocols using clomiphene citrate (CC) and subsequent gonadotrophin with mid-cycle administration of the GnRH antagonist cetrorelix (Cetrotide(R)) in IVF cycles. Rat pituitary cells were pretreated with CC, then stimulated with GnRH with and without co-administration of different concentrations of GnRH antagonist and compared with non-CC-pretreated controls. While lower concentrations of cetrorelix suppressed LH in CC-non-pretreated cells, but not in CC-pretreated cells, higher concentrations of cetrorelix suppressed LH in both groups. CC pretreatment increased the sensitivity of the pituitary for GnRH and reduced the efficacy of subsequent GnRH antagonist. Thus, the elevated risk of premature LH surges in clinical protocols using CC, gonadotrophin and GnRH antagonist could be overcome by increasing the antagonist dose.

Animals↗

Specific bone-protective effects of metabolites/derivatives of tamoxifen and clomiphene in ovariectomized rats.

In the ovariectomized (ovx) rat, the nonsteroidal antiestrogens, clomiphene (CLO) and tamoxifen (TAM), at dose levels that prevent development of osteopenia to a degree approaching that of 17beta-estradiol are, in contrast to 17beta-estradiol, only weakly uterotrophic. Metabolites of CLO and TAM might contribute differentially to these effects. Thus, we have evaluated bone protective and uterine effects in ovx rats of two such metabolites: 4-hydroxy CLO, produced by p-hydroxylation of CLO; and 4HTA, produced from TAM by stepwise replacement of its dimethylaminoethyl side chain with an acetic acid moiety, accompanied by p-hydroxylation. Also reported are effects of D4HTA, the dihydrodesethyl derivative of 4HTA previously characterized as a full estrogen mimetic in vitro. Administration of 4-hydroxy CLO (2.5 mg/kg subcutaneously) 5 days/week for 5 weeks to 3-month-old ovx rats resulted in complete prevention of bone loss and suppression of bone turnover to levels comparable to those of intact controls and to those of ovx animals similarly receiving 17beta-estradiol (10 microg/kg). However, uterine weight in animals receiving 4-hydroxy CLO was 64% less than that in 17beta-estradiol-treated animals. Although 4HTA (3.7 mg/kg s.c.) had a modest uterotrophic effect, it did not prevent bone loss associated with ovariectomy. In contrast, D4HTA (3.6 mg/kg s.c.) partially reduced bone turnover indicators and cancellous bone loss in a manner similar in many ways to that observed in TAM-treated ovx animals, but it had no uterotrophic effect. These results suggest that, although 4HTA does not contribute to the bone-protective effect of TAM, 4-hydroxy CLO might augment that of CLO.

Animals↗

Phenolic metabolites of clomiphene: [(E,Z)-2-[4-(1,2-diphenyl-2-chlorovinyl)phenoxy]ethyl]diethylamine. Preparation, electrophilicity, and effects in MCF 7 breast cancer cells.

The triarylethylene antiestrogen clomiphene was previously shown to undergo biotransformation to an active metabolite, 4-hydroxyclomiphene, and to 3-methoxy-4-hydroxyclomiphene plus the respective regioisomers of these, 4 and 5. We now report the synthesis and further chemical and biochemical studies on 3-5. Coupling of 4-[2-(diethylamino)ethoxy]benzophenone with either 4-(benzyloxy)benzaldehyde or its 3-methoxy analogue 11b in the presence of titanium, followed by chlorination and deprotection of the intermediate triarylethylenes, gave 4 and 5, respectively. Condensation of benzylmagnesium chloride with the (2-methoxyethoxy)methyl (MEM) ether of 4-[2-(diethylamino)ethoxy]-3'-methoxy-4'-hydroxybenzophenone, followed by mild acid treatment, afforded deschloro 3 due to facile MEM ether hydrolysis. Acetylation of this, followed by chlorination and deacetylation, gave 3. Compounds 4 and 5 reacted readily with nucleophiles. In particular, 2-mercaptoethanol reacted with 4 to afford deschloro vinyl thioether 13 as suggested by NMR spectral studies, a result that implicated allene-quinone 14 as the electrophilic species produced in solution from 4. Antiestrogen binding sites and estrogen receptors from MCF 7 human breast cancer cells interacted with 3 and 5 with affinities comparable to those of tamoxifen and 1, respectively; 5 was shown not to bind irreversibly with these sites. Inhibition of MCF 7 cell proliferation by 3-5 at 5 microM concentrations (76%, 57%, and 49%, respectively, relative to drug-free controls) compared favorably to that observed with 5 microM 1 (80%). These results suggest that 3-5 as well as 2 may contribute to the antiestrogenic effects of 1.

Binding, Competitive↗

Vascular endothelial growth factor concentrations in follicular fluid obtained from IVF-ET patients: a comparison of hMG, clomiphene citrate, and natural cycle.

PURPOSE: Evaluation of vascular endothelial growth factor (VEGF) concentrations of follicular fluid (FF) in accordance with an ovarian stimulation protocol and ovarian response. METHODS: The subjects of this study were 38 patients undergoing IVF-ET in our hospital. They were divided into three groups according to ovarian stimulation protocols; Group 1: hMG cycles (n = 19), Group 2: clomiphene citrate cycles (n = 10), Group 3: natural cycles (n = 9). They reclassified into three groups according to the number of oocytes harvested. VEGF concentration was measured in FF, employing ELISAs. RESULTS: Group 1 shows lower VEGF concentrations in FF than Group 2 or Group 3. Excluding high responders from Group 1, no difference was found among these three groups. As for the reclassified groups, group of highest number of oocytes havested showed lowest VEGF concentrations in FF. CONCLUSIONS: VEGF concentrations in FF might negatively correlate with the number of follicles, irrespective of the ovulation induction protocol.

Adult↗

Comparison of basal and clomiphene citrate induced FSH and inhibin B, ovarian volume and antral follicle counts as ovarian reserve tests and predictors of poor ovarian response in IVF.

PURPOSE: To compare basal and clomiphene citrate (CC) induced follicle-stimulating hormone (FSH), estradiol (E2), and inhibin B levels with ultrasound indices of ovarian reserve in infertile women and to test the prognostic value of these tests on response to ovarian stimulation in in vitro fertilization (IVF). METHODS: Fifty-six patients had basal and CC induced serum hormone levels and ultrasound measured mean ovarian volume (MOV) and mean antral follicle counts (MFC). Thirty-two patients were then appropriately selected to have a total of 41 cycles of IVF/ICSI treatment. RESULTS: Women with diminished ovarian reserve had lower MOV, MFC, day 3 and day 10 inhibin B levels (p < 0.001). Only basal and CC induced FSH and inhibin B correlated with MOV and MFC. Poor responders in IVF/ICSI had higher basal FSH (p < 0.05), lower basal and induced inhibin B levels (p < 0.05), and lower MOV and MFC (p < 0.01) than normal responders. Ovarian volume alone was better than age and basal hormones in predicting poor ovarian response, while abnormal CC test was the only independent significant factor in predicting ovarian response. However, age was the only independent predictor of pregnancy in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: CC test and ovarian volume are better than other hormonal and sonographic tests in predicting the response to ovarian stimulation in IVF cycles.

Adult↗

Predictive power of clomiphene citrate challenge test for failure of in vitro fertilization treatment.

BACKGROUND: To evaluate the impact of ovarian reserve on the outcome of in vitro fertilization (IVF) treatment in 140 women, in a total of 279 treatment cycles. METHODS: All women underwent a clomiphene citrate (CC) challenge test to assess their ovarian reserve before IVF treatment. One hundred and eighteen women (84%) had normal basal follicle stimulating hormone (FSH) levels (3.1-10.0 IU/l) and 22 women (16%) had elevated FSH levels (> 10.0-24.0 IU/l). The FSH levels measured on cycle day 10 showed that 106 (76%) of the women could be regarded as having a normal ovarian reserve and 34 (24%) a diminished ovarian reserve. RESULTS: In the group with diminished ovarian reserve, pregnancies and live births were dramatically lower than in the group with normal ovarian reserve. Counting only the first cycle (n = 140), the number of ongoing pregnancies and live birth rate were highly different between the two groups: 3% vs. 36% (1/33 vs. 28/78). Counting all treatment cycles (n = 210 + 69) the clinical pregnancy rate in the diminished ovarian reserve group was 6%-31% compared with the normal woman (4/69 compared 65/210). The number of started treatment cycles per woman were similar in the two groups. The length of the ovarian stimulations were slightly longer in the group with elevated FSH compared with the group with normal FSH levels. The number of cancellations resulting from insufficient ovarian response was significantly higher in the group with diminished ovarian reserve (n = 38, 55%) compared with the normal women (n = 32, 15%) (p < 0.0001). In addition, the average E2 levels before oocyte pick up were significantly lower in the group of women with diminished ovarian reserve compared with normal women (p < 0.0001). Calculation of the sensitivity and specificity of the CC test showed that an abnormal test has a high probability for a negative treatment outcome. The number of retrieved, fertilized oocytes, the number of divided oocytes, and the number of embryo transfers in the first as well as in all cycles differed significantly between the two of groups women (p < 0.001-0.009). CONCLUSIONS: We found that the CC challenge test is a useful tool in assessing a woman's ovarian capacity before infertility treatment. The predictive value of the test for a negative outcome of IVF treatment was strong. We recommend performing the test before infertility treatment. This may prevent unnecessary treatment trials and unrealistic expectations from both patients and doctors.

Clomiphene↗

The use of clomiphene citrate/human menopausal gonadotrophins in conjunction with GnRH antagonist in an IVF/ICSI program is not a cost effective protocol.

OBJECTIVE: To evaluate the cost effectiveness of a clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/GnRH antagonist protocol versus a long-acting GnRH agonist/hMG protocol. PARTICIPANTS AND METHODS: One hundred eighty nine couples having their first trial of ICSI for male factor infertility were divided into two groups. Group I (no = 33) received CC 100-150 mg/day for five days starting from day 2 of the cycle and 150 IU of hMG/day on days 6-10. GnRH antagonist (Centrorelix) 0.25 mg/day was started when the leading follicle reached 16 mm in the absence of an LH surge. Group II (no = 156) received 0.1 mg Deacapeptyl/day as our standard long protocol. RESULTS: Clinical pregnancy was observed in 8 out of the 33 cases in group I (24%) while in group II, 92 out of 156 achieved clinical pregnancy (59%), the difference was statistically significant (P = 0.019). The cost of medications/cycle was estimated to be 1110+/-492 E.P in group I, while it was 1928+/-456 E.P. in group II. However, the total cost per pregnancy was 19653 EP in group I and 10047 EP in group II. CONCLUSION: The use of the clomid/hMG/antagonist protocol is not a cost effective strategy and should not be recommended in IVF-ICSI cycles.

Adult↗

Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile.

Animals↗

Induction of artificial spermiation in the fresh water Clarias batrachus (Linn.) by clomiphene citrate.

Intramuscular thrice a week injections of clomiphene citrate (25 micrograms/0.5 ml/100 g body weight) were administered for a period of 3 months to the animals in the experimental group. The control group received 0.5 ml/100 g body weight of physiological saline throughout the period of experimentation (February - April). The control testes were in recrudescence in February, since spermatids and sperms came to appear in these testes from early March onwards. On the other hand, in the experimental group, as a result of drug administration, there was a steady increase in testicular size, and the spermatocytes begin to enlarge and mature into spermatids and sperms. This is to our knowledge, the first document of a commercially important male teleostean fish Clarias batrachus with high nutritive value being made to spermiate in the laboratory 4 months ahead of natural schedule, using a chemical inductor 'Clomid'.

Animals↗