Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans ; Azoospermia/therapy* ; Male ; Testosterone/therapeutic use* ; Anabolic Agents/adverse effects* ; Clomiphene/therapeutic use* ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Spermatogenesis/drug effects* ; Androgens/adverse effects*

OBJECTIVETo compare the difference in the therapeutic effects on ovulation disorder in polycystic ovary syndrome (PCOS) between the combined therapy of electroacupuncture and clomiphene and the single medication of clomiphene and to explore the effect mechanism.

METHODSA total of 80 patients of PCOS were randomized into an acupuncture plus medication group (40 cases) and a medication group (40 cases). In the medication group, since the 5th day of menstruation or medicine-withdrawal bleeding, clomiphene was prescribed for oral administration, continuously for 5 days. In the acupuncture plus medication group, the medication was the same as the medication group. Additionally, 30 min electroacupuncture (continuous wave, 2 Hz) was applied to Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1), Dahe (KI 12), Sanyinjiao (SP 6), Zhongji (CV 3), Diji (SP 8), Shenshu (BL 23), Sanjiaoshu (BL 22) and Ciliao (BL 32), etc. The treatment started on the 5th day of menstruation or medicine-withdrawal bleeding, once every two days, 3 times a week. One cycle of menstruation or 1 month was taken as one course. The treatment cycles were 3 months in the two groups. The level of estradiol (E) and progesterone (P) in the serum, the endometrial thickness and morphology, ovulation rate and clinical pregnancy rate, as well as the clinical therapeutic effects were compared after treatment in the two groups.

RESULTSTwo cases were dropped out because the herbal medicine was taken simultaneously in the acupuncture plus medication group. In the medication group, the medication was discontinued in 3 cases due to gastrointestinal adverse reactions. The total effective rate was 86.8% (33/38) in the acupuncture plus medication group, better than 64.9% (24/37) in the medication group (<0.05). The ovulation rate in the acupuncture plus medication group was higher than that in the medication group [(86.8%, 33/38) vs (64.9% 24/37), <0.05]. The pregnancy rate in the acupuncture plus medication group was higher than the medication group in tendency, without significant difference [21.1% (8/38) vs 16.2% (6/37), >0.05]. After treatment, the results of endometrial thickness and morphology (A-type rate) in the acupuncture plus medication group were better than those in the medication group (<0.01, <0.05). After treatment, regarding the levels of E and P in the serum in the window period of implantation, the results in the acupuncture plus medication group were higher remarkably than those in the medication group (both <0.01).

CONCLUSIONThe combined intervention of electroacupuncture and clomiphene achieves the definite effects of ovulation and pregnancy promotion in PCOS. It remarkably increases the levels of E and P in the serum, the endometrial thickness and A-type rate. The therapeutic effects of the combined intervention are remarkably better than those of the simple application of clomiphene. This combined intervention is safe and tolerable for the adverse reactions. The effect mechanisms may be related to the improvements of estrogen, progestin and endometrial receptivity.

Acupuncture Therapy ; Clomiphene ; therapeutic use ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Infertility, Female ; therapy ; Ovulation ; Ovulation Induction ; Polycystic Ovary Syndrome ; therapy ; Pregnancy ; Pregnancy Rate

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.
Adult ; Chromatography, High Pressure Liquid ; Clomiphene/blood/metabolism/*therapeutic use ; Cytochrome P-450 CYP2D6/*genetics ; Estrogen Antagonists/analysis/metabolism/therapeutic use ; Female ; Genotype ; Humans ; Infertility/*drug therapy/genetics ; Ovulation Induction ; Phenotype ; *Polymorphism, Genetic ; Republic of Korea ; Tandem Mass Spectrometry

OBJECTIVETo explore the molecular biological mechanism of ZHU's Tiaojing Cuyun Recipe (TCR) for treating anovulatory infertility patients with Shen deficiency syndrome (SDS) by observing its clinical efficacy.

METHODSUsing randomized blocking methods, 80 patients were assigned to the treatment group (40 cases) and the control group (40 cases). Patients with regular menstrual cycle started medication from the 5th day of menstruation. Those with irregular menstrual cycle first took progesterone till withdrawal bleeding ,and then started medication from the 5th day of vaginal bleeding. Patients in the treatment group took ZHU's TCR, one dose per day, while those in the control group took Clomifene Citrate (CC), 50 mg per day. Three menstrual cycles consisted of one therapeutic course, a total of 2 courses. Clinical efficacy such as pregnancy rates and abortion rates were observed. Ovulation indices (the maximal diameter of mature follicles, luteinized follicles, ovulational follicles, and the endometrial thickness on the ovulation day), SDS, and integrals of menstrual symptoms were monitored before and after treatment. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) , and estradiol (E2) were determined using chemiluminescent immunoassay before treatment and after on therapeutic course. Serum levels of activin A (ACTA), inhibin B (INHB), and follistatin (FS) were detected using double antibody sandwich ELISA.

RESULTSCompared with the control group, the pregnancy rate was obviously elevated and the abortion rate was obviously lowered in the treatment group (P <0. 05). Ovulation rates of mature follicles and luteinizing follicles decreased more in the treatment group (P < 0.05). Compared with before treatment, integrals for SDS were lower, the maximal diameter of pre-ovulational follicles was increased, and integrals for menstrual symptoms in non-pregnant patients of the two groups were obviously lowered. Meanwhile, the endometrial thickness on the ovulation day was increased in the treatment group after treatment, but reduced in the control group (P < 0.05, P < 0.01). Compared with the control group, integrals for SDS were decreased, and the maximal diameter of pre-ovulational follicles was lowered in the treatment group after treatment (P < 0.05, P < 0.01). Integrals for SDS and the difference in the endometrial thickness on the ovulation day were increased, but the difference in the maximal diameter of pre-ovulational follicles were reduced (P < 0.05, P < 0.01). In the treatment group serum levels of E2 and ACTA increased more after one therapeutic course than before treatment (P < 0.01), but serum levels of INHB and FS decreased more after one therapeutic course than before treatment (P < 0.05). In the control group serum levels of FSH and ACTA increased more, and the serum level of FS decreased more after one therapeutic course than before treatment (P < 0.05, P < 0.01). Compared with the control group, serum levels of FSH and ACTA increased more, and serum levels of INHB decreased more in the treatment group after one therapeutic course than before treatment (P < 0.05, P < 0.01).

CONCLUSIONSZHU'sTCR could improve SDS of anovulatory infertility patients, regulate the follicular development, and elevate the pregnancy rate. Its actions might be associated with regulating their sex hormones, expressions of ovary local factors such as INHB, ACTA, and FS.

Activins ; Clomiphene ; Drugs, Chinese Herbal ; therapeutic use ; Estradiol ; Female ; Follicle Stimulating Hormone ; Follistatin ; Humans ; Infertility, Female ; complications ; therapy ; Inhibins ; Luteinizing Hormone ; Medicine, Chinese Traditional ; Ovarian Diseases ; Ovarian Follicle ; Ovulation ; Progesterone

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

OBJECTIVETo observe the therapeutic effect of Qilin Pills combined with clomiphene on idiopathic oligoasthenospermia.

METHODSWe randomly assigned 300 patients with idiopathic oligoasthenospermia to a trial (n = 156) and a control group (n = 144) to be treated with Qilin Pills (6 g, tid) combined with clomiphene (50 mg, qd) and clomiphene alone (50 mg, qd), respectively, both for a course of 12 weeks. Before and after 4, 8, and 12 weeks of medication, we determined sperm concentration, the percentages of grade a and grade a + b sperm, sperm motility, and the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T), followed by evaluation of the clinical efficacy of Qilin Pills with the pregnancy rate in the patients' spouses as the secondaty therapeutic indexes.

RESULTSCompared with the baseline, both groups of patients showed remarkably improved semen parameters and hormone levels after treatment (all P < 0.01). After 4, 8, and 12 weeks of medication, statistically significant differences were observed between the trial and control groups in sperm concentration ([17.06 ± 2.24] vs [15.07 ± 2.48], [22.10 ± 2.65] vs [18.11 ± 2.97], and [28.13 ± 3.59] vs [21.21 ± 3.60] x 10(6)/mL, P < 0.01), the percentage of grade a sperm ([15.03 ± 2.39] vs [13.08 ± 2.51], [21.08 ± 3.16] vs [16.04 ± 3.05], and [28.08 ± 4.70] vs [20.14 ± 4.74]%, P < 0.01), the percentage of grade a + b sperm ([30.10 ± 5.07] vs [26.21 ± 3.96], [38.08 ± 5.64] vs [30.07 ± 4.80], and [48.04 ± 6.49] vs [35.28 ± 4.77]%, P < 0.01), sperm motility ([42.04 ± 4.86] vs [40.29 ± 4.19], [52.05 ± 5.58] vs [48.03 ± 4.40], and [65.03 ± 5.13] vs [56.67 ± 4.99]%), the FSH level ([7.75 ± 1.38] vs [7.20 ± 1.17], [10.83 ± 1.23] vs [9.10 ± 1.32], and [14.22 ± 0.84] vs [12.06 ± 1.45] IU/L, P < 0.01), the LH level ([10.05 ± 1.68] vs [9.18 ± 1.54], [13.96 ± 1.68] vs [11.99 ± 1.71], and [19.01 ± 2.42] vs [15.86 ± 2.08] IU/L, P < 0.01) and the T level ([19.19 ± 192] vs [18.34 ± 1.79] [21.06 ± 1.63] vs [20.06 ± 1.56], and [24.63 ± 1.06] vs [22.03 ± 1.49] nmol/L, P < 0.01). The pregnancy rate in the patients' spouses was significantly higher in the trial than in the control group at 4, 8, and 12 weeks (1.92 vs 0.69, 4.81 vs 3.47, and 11.54 vs 8.33%, P < 0.01). There were no statistically significant differences in drug tolerance between the two groups (P > 0.05). No obvious adverse reactions were observed.

CONCLUSIONQilin Pills combined with clomiphene can evidently improve the seminal quality and hormone level of oligoasthenospermia patients with no obvious adverse events. However, its long-term efficacy and tolerance deserve further clinical investigation.

Asthenozoospermia ; blood ; drug therapy ; Clomiphene ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fertility Agents ; therapeutic use ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Male ; Pregnancy ; Pregnancy Rate ; Semen ; Sperm Count ; Sperm Motility ; Spermatozoa ; Testosterone ; blood

INTRODUCTIONIntrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) was applied to selected infertile patients to determine the effect of gonadotropin-releasing hormone (GnRH) antagonists in IUI cycles, in which recombinant follicle-stimulating hormone (rFSH) had been used for COH.

METHODSThis study was conducted between April 1, 2009 and June 10, 2009, and involved a total of 108 patients. These patients had primary or secondary infertility, which resulted in an indication for IUI, and they each received two cycles of ovarian stimulation treatment with clomiphene citrate. The patients were randomised into two groups--patients in group A received rFSH + GnRH antagonist (n = 45), while those in group B received only rFSH (n = 63).

RESULTSThe mean age of the patients was 31.84 ± 3.73 years and the mean body mass index (BMI) was 24.40 ± 1.88 kg/m(2). The mean age and BMI of the patients in groups A and B were not significantly different. There was no significant difference in the mean total rFSH dose administered (988.33 IU in group A and 871.83 IU in group B). When compared to group B, the mean number of follicles that were > 16 mm on the human chorionic gonadotropin (HCG) trigger day was significantly higher in group A (1.58 and 1.86, respectively; p < 0.05). When the two groups were compared, there were no statistically significant differences in the number of cancelled cycles due to premature luteinisation (none in group A vs. two in group B) and the rate of clinical pregnancy (8.9% in group A vs. 7.9% in group B).

CONCLUSIONNo significant improvement in the clinical pregnancy rates was observed when GnRH antagonists were used in COH + IUI cycles, despite the significant increase in the number of follicles that were > 16 mm on HCG trigger day.

Adult ; Body Mass Index ; Chorionic Gonadotropin ; blood ; Clomiphene ; therapeutic use ; Endometrium ; pathology ; Female ; Follicle Stimulating Hormone ; therapeutic use ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Hormone Antagonists ; therapeutic use ; Humans ; Infertility, Female ; therapy ; Insemination, Artificial ; methods ; Ovulation Induction ; methods ; Pregnancy ; Pregnancy Rate ; Young Adult

OBJECTIVETo study the effect and potential mechanism of Modified Cangfu Daotan Decoction (MCDD) on endometrial receptivity in infertility patients with polycystic ovarian syndrome (PCOS).

METHODSTotally 298 women having normal ovulation who underwent artificial insemination were recruited as the control group, and they received no drug therapy. Another 355 infertility patients with PCOS who received ovarian stimulation therapy were recruited as the treatment group. Then they were further assigned to the treatment group I (195 cases) and the treatment group II (160 cases) according to random digit table. Patients in the treatment group I received clomiphene (CC) + human menopause gonadotropin (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II received CC + HMG + HCG and additionally took modified MCDD. The therapeutic course for all was three menstrual cycles. The pregnancy ratio, the endometrial thickness, and spiral artery pulsatility index (PI), resistance index (RI), and homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot.

RESULTSCompared with the control group, the endometrial thickness decreased and PI and RI increased in the treatment group I (all P < 0.05). Compared with the treatment group I , the endometrial thickness increased and PI and RI decreased in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR levels were significantly decreased in the treatment group II after treatment (P < 0.05). Compared with the control group before treatment, the HOMA-IR level increased in the treatment group I and the treatment group II before treatment (P < 0.05). Compared with the control group after treatment, the HOMA-IR level increased in the treatment group I (P < 0.05). But there was no statistical difference in the post-treatment HOMA-IR level between the control group and the treatment group II (P < 0.05). Compared with the control group, the post-treatment UCP2 level was increased in the treatment group II (P < 0.05). After one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group, 23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment group II. Compared with the control group, the pregnancy rate was significantly increased in the treatment group II (P < 0.05).

CONCLUSIONMCDD was found to be capable of increasing the pregnancy rate of infertility patients with PCOS, which might be associated with improving endometrial blood flow and insulin resistance, increasing the UCP2 expression, and finally improving the endometrial receptivity.

Chorionic Gonadotropin ; Clomiphene ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gonadotropins ; Humans ; Infertility ; Infertility, Female ; Insulin Resistance ; Ovulation ; Ovulation Induction ; methods ; Polycystic Ovary Syndrome ; drug therapy ; Pregnancy ; Pregnancy Rate

INTRODUCTIONSuperovulation-intrauterine insemination (SO-IUI) is the most common assisted reproductive technique (ART) in the world, with good evidence of efficacy and cost-effectiveness. However, parameters affecting its success have not been consistently reported. So in this study, we aim at determining the parameters influencing the success rate of SO-IUI.

MATERIALS AND METHODSWe conducted a retrospective cohort study of 797 SO-IUI cycles from 606 patients, performed between 2007 and 2009 in a single centre. These women received clomiphene citrate (CC), recombinant FSH (rFSH) or both.

RESULTSThere were 127 clinical pregnancies with a pregnancy rate (PR) of 15.9% (127/797) per treatment cycle. Factors associated with higher PR included maternal age <38 (P = 0.02), subfertility diagnoses of ovulatory disorders, unexplained infertility, sexual dysfunction and unilateral tubal obstruction (P = 0.02), an endometrial thickness ≥8 mm (P = 0.03), total number motile spermatozoa (TNMS) of ≥1 million (P = 0.03), and spermatozoa normal forms (NF) ≥4% (P <0.01) on bivariate analysis. When CC is used, the endometrial thickness is more likely to be suboptimal (<8 mm). All the above parameters remained significant except the subfertility diagnoses on multivariate analysis.

CONCLUSIONPatients' selection with women <38 years old and preferably with ovulation disorders and unexplained infertility is associated with the highest PR in SO-IUI. Cycle parameters such as the use of rFSH alone, with the avoidance of CC, TNMS ≥1 million and NF ≥4% is likely to result in the best outcomes and reduce the high order multiple pregnancy risk.

Adult ; Age Factors ; Clomiphene ; therapeutic use ; Cohort Studies ; Female ; Fertility Agents, Female ; therapeutic use ; Humans ; Infertility, Female ; etiology ; Insemination, Artificial ; methods ; Pregnancy ; Pregnancy Rate ; Prognosis ; Retrospective Studies ; Superovulation