Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

Pituitary suppression protocol among Bologna poor responders undergoing ovarian stimulation using corifollitropin alfa: does it play any role?

RESEARCH QUESTION: Does the type of pituitary suppression protocol influence cumulative live birth rate (LBR) in Bologna poor responders treated with corifollitropin alfa (CFA)? DESIGN: Retrospective cohort analysis including poor responder patients fulfilling the Bologna criteria who underwent their first intracytoplasmic sperm injection cycle using a CFA-based ovarian stimulation protocol between 2011 and 2017. The starting dose of CFA was 150 µg. The primary outcome was cumulative LBR, defined as the first delivery of a live born resulting from the fresh and all the subsequent frozen embryo transfers. RESULTS: A total of 717 cycles were divided into three groups: A (gonadotrophin-releasing hormone [GnRH] antagonist protocol, n = 407), B (long GnRH agonist protocol, n = 224) and C (short GnRH agonist protocol, n = 86). Cumulative LBR did not significantly differ between groups (20.1% versus 17.4% versus 14.0%; P = 0.35). Significantly more patients in Group A had supernumerary embryos cryopreserved (28.3% versus 18.4% versus 11.6%; P < 0.001). Days of additional highly purified human menopausal gonadotrophin 300 IU injections following CFA were significantly different between Groups A, B and C (3 versus 5 versus 3 days; P < 0.001). Multivariate logistic regression analysis showed that the number of oocytes retrieved remained an independent predictive factor (odds ratio 1.23, 95% confidence interval 1.16-1.31) for cumulative LBR. CONCLUSIONS: Poor responders according to the Bologna criteria in whom CFA is used for ovarian stimulation had comparable cumulative LBR, irrespective of the type of pituitary suppression. An increase in number of oocytes retrieved is an independent variable related to cumulative LBR.

Safety data for the use of nasal human menopausal gonadotropins: a potential novel approach for fertility treatment.

Some of the common side effects of the injectable gonadotropins, used during fertility treatments, are pain at the injection site, skin erythema, muscle pain, and rarely vasovagal reflex. These side effects cause inconvenience and lower patient's tolerance for fertility treatments.The purpose of this study was to evaluate the safety and efficacy of an FDA-approved dose of nasal human menopausal gonadotropins (Menopur) in women undergoing fertility treatment. Healthy regularly cycling reproductive-aged women (n=4) with infertility were enrolled. A total of 75 IU of each Menopur bottle was dissolved and placed in a nasal pump spray device (concentration of 3.75 IU/spray). Each participant was allowed to inhale a total of 2 sprays daily after which ovarian response during the follicular phase was monitored by transvaginal ultrasound and serum hormone measurement. None of the participants reported any side effects at the nasal site of drug administration. No known common side effects of the Menopur drug were reported by any of the participants. Despite adequate absorption of the nasal Menopur, as confirmed by elevated serum FSH levels while taking the nasal medication, 3 out of 4 participants did not show any follicular growth until cycle day 13 while only one participant who agreed to continue taking the medication until cycle day 20 developed one dominant follicle and had elevated serum estradiol levels. This FDA approved case series suggest that nasal route of Menopur administration seems to be safe at a very low doses and it constitutes a potential novel approach for ovarian stimulation.

Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

OBJECTIVE: This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. METHODS: This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged < 40 years submitted to COS with corifollitropin alfa 100µg or 150µg (n = 26) and rFSH or HP-HMG in the first seven days of treatment with daily doses of 150-225 IU (n = 106); all subjects were on GnRH antagonist protocols. RESULTS: The groups had similar mean ages and duration of stimulation. The mean number ± standard deviation of total aspirated oocytes and MII oocytes was 11.9±10 and 10.3±7.9 in the corifollitropin alfa group, and 10.9±7.2 and 8.6±5.7 in the group on rFSH or HMG (p>0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. CONCLUSIONS: Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

[Comparison of results of two flexible ovarian hiperestimulation protocols with two different initial doses (150 vs ≥ 225)]. / Comparación de los resultados de dos protocolos flexibles de hiperestimulación ovárica controlada con dos dosis diferentes de inicio (150 vs ≥ 225).

BACKGROUND: With the use of new protocols Controlled ovarian hyperstimulation (COH) with lower doses of gonadotropins to the classics protocols and current trend of fewer embryos transferred, there is no agreement until today on the optimal dose start of a COH protocol. OBJECTIVE: Compare the results of two flexible protocols of HOC with different starting doses (150 vs 225 lU rFSH/hMG) plus a GnRH antagonist in cycles of IVF / ICSI. METHODS: Retrospective, descriptive study, we analyzed 231 cycles of IVF/ICSI being the primary variables: total FSH dose, dose increase, retrieved oocytes, embryos available for transfer and for cryopreservation. RESULTS: The total dose of FSH in group 11 was significantly higher versus group 1 (2096.0 vs 1447.9). The percentage of patients in whom the dose increased was higher in Group I vs Group 11 (26.4% vs 9.1%, p = 0.001). The number of retrieved oocytes was similar between the groups (10.5 vs 10.2, p = 0.76) as well as the number of embryos available the day of the transfer and the number of embryos that were vitrified 6.73 vs 6.08 (p = 0.97) and 1.5 and 1.3 (p=0.820) for Group I and I respectively. The clinical pregnancy rate was 39.3% (n = 91), and for groups I and 11 were 41.6 and 37.7% respectively. CONCLUSIONS: No significant differences between two loading dose was found (150 vs ≥ 225) in most of the primary endpoint.

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection.

BACKGROUND: Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. METHODS: A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. RESULTS: Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. CONCLUSION: Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG.

Effect of the oral contraceptive pill on patients undergoing controlled ovarian hyperstimulation.

This is a retrospective analysis of 89 patients who were undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer in the Fertility Management Unit of the Department of Obstetrics, Gynaecology and Child Health, The University of the West Indies. Twenty-eight patients (Group A), who did not receive oral contraceptive pills prior to controlled ovarian hyperstimulation (COH) were compared with 61 patients in Group B treated with oral contraceptive pills for two months prior to undergoing COH assisted reproduction using the long protocol. The number of follicles, oocytes, estimated oestradiol levels on the day of administration of human chorionic gonadotrophin (hCG), pregnancy rates, miscarriage rates and the incidence of patients who developed ovarian hyperstimulation syndrome (OHSS) were the main outcome measures. The mean age and haematocrit were the same in each group. The number of follicles retrieved tended to be higher in Group A than in Group B (median 8 versus 6, p = 0.06) with significantly more oocytes being retrieved in Group A than Group B (p < 0.05). There were no statistically significant differences between the two groups in oestradiol levels, the proportion of patients with polycystic ovarian disease, the proportion of women who developed ovarian hyper-stimulation syndrome or pregnancy outcomes. There was no difference between the groups in measures of clinical severity of OHSS. In a logistic regression model the significant predictors of OHSS were haematocrit and oestradiol levels. There appeared to be no significant clinical benefit in administering oral contraceptive pills for two months to patients prior to COH.

Effect of the oral contraceptive pill on patients undergoing controlled ovarian hyperstimulation

This is a retrospective analysis of 89 patients who were undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer in the Fertility Management Unit of the Department of Obstetrics, Gynaecology and Child Health, The University of the West Indies. Twenty-eight patients (Group A), who did not receive oral contraceptive pills prior to controlled ovarian hyperstimulation (COH) were compared with 61 patients in Group B treated with oral contraceptive pills for two months prior to undergoing COH assisted reproduction using the long protocol. The number of follicles, oocytes, estimated oestradiol levels on the day of administration of human chorionic gonadotrophin (hCG), pregnancy rates, miscarriage rates and the incidence of patients who developed ovarian hyperstimulation syndrome (OHSS) were the main outcome measures. The mean age and haematocrit were the same in each group. The number of follicles retrieved tended to be higher in Group A than in Group B (median 8 versus 6, p = 0.06) with significantly more oocytes being retrieved in Group A than Group B (p < 0.05). There were no statistically significant differences between the two groups in oestradiol levels, the proportion of patients with polycystic ovarian disease, the proportion of women who developed ovarian hyper-stimulation syndrome or pregnancy outcomes. There was no difference between the groups in measures of clinical severity of OHSS. In a logistic regression model the significant predictors of OHSS were haematocrit and oestradiol levels. There appeared to be no significant clinical benefit in administering oral contraceptive pills for two months to patients prior to COH

Serum inhibin levels before and after gonadotropin stimulation in cryptorchid boys under age 4 years.

We evaluated eleven cryptorchid boys under four years of age to determine the usefulness of serum inhibin as a marker of seminiferous tubule dysfunction. Serum testosterone, inhibin, LH and FSH concentrations were measured by RIA before and after 6 weeks of human chorionic gonadotropin plus human menopausal gonadotropin therapy, and bilateral testicular biopsies were performed at orchiopexy. Hormonal results from the cryptorchid group were compared to those from an age-matched control group. Basal LH and testosterone levels were similar in the two groups. Cryptorchid boys had lower basal inhibin and higher FSH levels than controls. After gonadotropin treatment the inhibin/FSH ratio was lower in cryptorchid than control children, suggesting the presence of seminiferous tubule damage (p = 0.002). Normal numbers of spermatogonia were seen in 6/9 scrotal and in 1/13 cryptorchid testes. The peak of inhibin was positively correlated to the number of spermatogonia (r = 0.68; p = 0.02). We conclude that basal and stimulated inhibin concentrations, as well as basal and stimulated inhibin/FSH ratio, provide additional information on seminiferous tubule function in cryptorchid boys and can be useful to evaluate Sertoli cell function in these patients.

Successful birth after intrafallopian transfer of microhatched embryos.

OBJECTIVE: To present a successful transfer of microhatched embryos to the fallopian tubes via microlaparoscopy. DESIGN: Case report. SETTING: Private practice affiliated with a medical university. PATIENT: A 40-year-old woman with primary infertility, mildly elevated baseline FSH levels, and a history of poor ovarian response to ovulation induction. Her husband had severe oligoospermia after vasectomy reversal. INTERVENTION(S): Late luteal leuprolide acetate to pituitary down-regulation followed by pure FSH, 300 IU, and hMG, 300 IU, daily for ovulation induction. Transvaginal oocyte retrieval, intracytoplasmic sperm injection, assisted embryo hatching, microlaparoscopic intrafallopian ET. MAIN OUTCOME MEASURE(S): Amniocentesis at the 14th week of gestation revealed a normal karyotype (46,XX), birth of a normal female infant (3700 g). RESULT(S): Establishment of a single, viable intrauterine gestation followed by a vaginal delivery at term. CONCLUSION(S): This case shows the possibility of using assisted-hatched embryos for laparoscopic intrafallopian tube transfer.

O emprego do citrato de clomifeno e gonadotrofina de mulher menopausada como alternativa de hiperestimulaçäo ovariana em pacientes com resposta idiopática inadequada na fertilizaçäo in vitro / Clomiphene citrate and gonadotropins of woman in menopause as an alternative approach to ovarian hyperstimulation in idiopatic poor response for in vitro fertilization

OBJETIVO: Avaliar os efeitos do esquema de estimulaçäo ovariana com citrato de clomifeno (CC)/gonadotrofina de mulher menopausada (hMG) nos resultados da fertilizaçäo in vitro e transferência de embriöes (FIVETE) em um grupo de pacientes que apresentaram resposta ovariana inadequada em ciclos prévios de FIVETE estimulados com um análogo do GnRH e gonadotrofinas (protocolo longo). MÉTODO: Os resultados de FIVETE em ciclos estimulados com CC/hMG e com o protocolo longo de uma mesma paciente foram comparados. Oito pacientes (grupo I) que apresentaram uma resposta ovariana idiopática inadequada (idade: < 38 anos, FSH<15 mU/mL, E2<60pg/mL, ciclos menstruais regulares e ausência de cirurgia ovariana) ao protocolo longo em 11 ciclos de FIVETE (grupo Ia), foram estimuladas com CC/hMG em 20 ciclos (grupo Ib). Administrou-se CC 100 mg/dia por 5 dias a partir do 3§ dia do ciclo e o hMG 150 UI/dia foi iniciado no 5§ dia, sendo a dose modificada de acordo com a resposta da paciente. Dezenove ciclos de 15 pacientes com resposta ovariana adequada ao protocolo longo, durante o mesmo intervalo de tempo, foram incluídas neste estudo como grupo controle (grupo II). Casais com fator masculino de infertilidade foram excluídos. RESULTADOS: As pacientes avaliadas näo apresentaram diferença em termos de idade, duraçäo da infertilidade e do índice de massa corpórea. Embora a duraçäo do estímulo ovariano tenha sido similar nos 3 grupos: 10,1 + 0,76, 10,9 + 0,34 e 10,3 + 0,21 dias para os grupos Ia, Ib e II, respectivamente, o número médio de ampolas de hMG utilizado no grupo Ib (13,6 + 1,36) foi significativamente menor (p<0.001) quando comparado aos grupos Ia e II (49,9 + 3,20, 43,7 + 2,73; respectivamente). A taxa de cancelamento foi de 36,4 por cento, 25,0 por cento e 0 por cento (grupos Ia, Ib e II; respectivamente), näo revelando diferença entre os grupos Ia e Ib. Os números médios de oócitos MII inseminados e fertilizados foram de 4,9 + 0,8 e 1,3 + 0,4 no grupo Ia e de 4,4 + 0,3 e 2,1 + 0,2 no grupo Ib, näo mostrando diferença entre os grupos. Contudo, os números médios de oócitos MII inseminados e fertilizados no grupo II, 11,4 + 2,0 (p<0.01) e 7,9 + 2,0 (p=0.01), respectivamente, foram significativamente maiores quando comparados aqueles do grupos Ia e Ib...

Factores pronósticos de la inseminación intrauterina en el tratamiento de la infertilidad / Prognostic factors of the intrauterine insemination in the infertility treatment

Se revisan retrospectivamente 407 ciclos de inseminación intrauterina con semen del marido con el objeto de determinar factores pronósticos del procedimiento y el número de ciclos a realizar. Se encontró una diferencia significativa al comparar edad y años de infertilidad entre ciclos concepcionales y no concepcionales. Hubo un 3 por ciento de embarazos por ciclos con recuentos < 1 millón de espermatozoides móviles inseminados (EMI). El 97,7 por ciento de los embarazos se lograron en los primeros 4 ciclos, con una tasa acumulativa de 0,387. Se concluye que la IIU tiene mejor pronóstico en pacientes menores de 35 años, con una infertilidad menor de 5 años. El procedimiento no se justifica con recuentos menores a 1 milllón de EMI, y se sugiere no realizar más de 4 ciclos de tratamiento

[Ovarian hyperstimulation with menotropins as treatment for unexplained sterility; effect of reproductive characteristics on the results]. / Hiperestimulación ovárica con menotropinas como tratamiento para la esterilidad inexplicable; efecto de las características reproductivas en los resultados obtenidos.

The objective was to evaluate the utility of the ovarian hyperstimulation with menotropins as treatment of unexplained infertility. One hundred couples with unexplained infertility were treated. Ovarian stimulation was started with 150 IU of menotropins on day 3 of the menstrual cycle, monitoring the follicular growth with transvaginal ultrasonography, additional doses of menotropins were administered accordingly. Human chorionic gonadotropin (10000 IU) was administered when the dominant follicle reached a diameter > or = 16 mm. The pregnancy rate per cycle was 12.0%, on the other hand the cumulate rate of pregnancy was 48.0%. The age under 30 years and the antecedent of previous pregnancies were correlated with the likelihood of conception. The spontaneous abortion rate was 35.4%. As conclusion, it therefore appears appropriate, to offer a treatment with menotropins to that specific group of couples with unexplained infertility with good prognostic factor as age < 30 years and infertility duration < 5 years. The increase on the spontaneous abortion rate was probably induced for the luteal insufficiency produced by the ovarian hyperstimulation with menotropins.

Factores que influyen en el logro del embarazo en pacientes con disfunción hipotálamo-hipófisis tratadas con menotropinas / Factors which influence the success of pregnancy in patients with hypothalamohypophysis dysfunctions treated with menotropins

Se resaltan las características que deben tener las pacientes sometidas a inducción de ovulación con gondotropina menopáusica humana, debido a que es un buen método para el logro de embarazo en pacientes con anovulación crónica en las que se han descartado otras causas de esterilidad. Se incluyeron 32 pacientes que ingresaron al Departamento de Ginecología Endocrinológica, Hospital de Ginecoobstetricia Núm. 3 del Centro Médico Nacional La Raza, durante un año. Se obtuvo la ovulación esperada en todas las pacientes incluidas (100 por ciento), con un total de 13 embarazos (40.6 por ciento), lo que concuerda con otros trabajos informados previamente. Se formaron dos grupos. En el grupo I, se incluyeron 12 pacientes candidatas ideales, menores de 30 años de edad, peso adecuado, sin otros factores de esterilidad. En el grupo II, se incluyeron 20 pacientes con el mismo diagnóstico, mayores de 30 años de edad, con obesidad y algún otro factor de esterilidad agregado. En el grupo I, se lograron nueve embarazos (75 por ciento); en el grupo II, cuatro (20 por ciento). Se considera que las características que deben predominar en las pacientes atendidas por esterilidad para asegurar un mayor éxito son: mujeres con disfunción del factor neuroendocrino puro, índice de masa corporal normal o bajo (15 a 20 por ciento) y edad entre 25 a 29 años. No se encontró diferencia significativa en la influencia del grosor endometrial.

Padröes de desenvolvimento folicular em ciclos espontâneos e induzidos de pacientes inférteis portadoras de endometriose pélvica leve / Follicle growth patterns in spontaneous and induced cycles in infertili women with mild endometriosis

OBJETIVOS: avaliar os padroes de desenvolvimento folicular em ciclos espontâneos (CE) e os efeitos da hiperestimulaçao ovariana controlada com citrato de clomifeno (CC) e/ou gonadotrofina de mulher menopausada (HMG) e gonadotrofina coriônica humana (HCG) sobre a foliculogênese e taxas de gestaçao de pacientes inférteis portadoras de endometriose leve. MÉTODO: A avaliaçao sonográfica transvaginal seriada da dinâmica folicular foi realizada em 88 ciclos (CE, 21; CC/HMG/hCG, 29; HMG/HCG, 38) de 19 pacientes inférteis portadoras de endometriose pélvica (grupo de estudo) em comparaçao com 98 ciclos (CE, 27; CC/hMG/ hCG, 42; hMG/hCG, 29) de 21 casais portadores de infertilidade masculina (grupo controle). RESULTADOS: Foliculogênese normal foi observada em 50 (56.8 por cento) ciclos do grupo de estudo e em 88 (89.8 por cento) ciclos do grupo controle (p

The empty follicle syndrome: a pharmaceutical industry syndrome.

The purpose of this study is to provide evidence that empty follicle syndrome (EFS) is a result of an abnormality in the in-vivo biological activity of some batches of commercially available human chorionic gonadotrophin (HCG). This is a comparative study between six consecutive in-vitro fertilization (IVF) cases with EFS (study group) and 10 IVF pregnancy cycles (control group). Both groups received the same ovarian stimulation protocol consisting of leuprolide acetate and human menopausal gonadotrophin (HMG). An i.m. injection of 10,000 IU of HCG was administered once follicles had reached 18-20 mm and oestradiol/follicle > or = 16 mm was at least 900 pmol/l. Transvaginal aspiration was performed 36 h later. Plasma HCG prior to and 12 h after i.m. injection as well as the follicular fluid (FF) concentrations of oestradiol, progesterone, luteinizing hormone (LH) and HCG were determined in the study group and controls. The in-vitro biological activity of the batch of HCG used by the EFS cases and the control group was determined using a Leydig cell preparation from adult rats. Furthermore, the plasma clearance rate after i.v. injection of 5000 IU of HCG, from the same batches, was studied in three male volunteers. In the IVF cycles, no HCG was detected in plasma prior to the injection of commercial HCG. After 12 h, no HCG was detected in the study group compared to a mean of 207.5 IU/l (110-360) in controls. Mean FF concentration of LH, HCG, progesterone and oestradiol was 0.9 IU/l, 0 IU/l, 3.1 nmol/ml and 4.4 nmol/ml in EFS compared to 1.0, 98.3, 32.0 and 3.7 in pregnancy cycles. The in-vitro biological activity in both HCG batches was not significantly different; however, immunoreactive HCG used in EFS cases was undetectable in plasma of male volunteers as soon as 10 min after i.v. injection of 5000 IU of HCG. The endocrine abnormalities found in follicular fluids of EFS are not a consequence of an ovarian problem but the result of a lack of exposure to biologically active HCG. The rapid clearance of the drug after i.v. injection and the high affinity of desialylated HCG to liver cells suggest this to be a possible explanation for this infrequent but unfortunate event.