Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.     

High-dose follicle-stimulating hormone stimulation at the onset of the menstrual cycle does not improve the in vitro fertilization outcome in low-responder patients

In an attempt to improve their outcome with in vitro fertilization (IVF), 34 low-responder patients were stimulated with six ampules of follicle-stimulating hormone (FSH) daily starting on day 1 (n = 17) or day 2 (n = 17) of their menstrual cycles. The stimulated cycles showed a mean peak estradiol of 443 +/- 173 pg/mL, mean days of human chorionic gonadotropin of 7.6 +/- 1.4, 2.67 +/- 1.5 preovulatory oocytes per retrieval, and 2.56 +/- 1.3 oocytes per transfer. Three clinical pregnancies resulted after 25 embryo transfer cycles (12%). With paired analysis, we compared 8 patient cycles with prior six ampules of FSH stimulation starting on day 3; all parameters examined showed no significant differences. In a comparison of 22 patient cycles with prior 4 ampules of FSH stimulation on cycle day 3, no significant differences in any parameters were observed except in the higher number of ampules used in the present study. We conclude that high-dose FSH stimulation at the onset of the menstrual cycle does not improve the IVF outcome in low-responder patients.     

Inhibin B and anti-Mullerian hormone: markers of ovarian response in IVF/ICSI patients?

OBJECTIVE: The objective of this study was to investigate whether follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH) and inhibin B could be useful in predicting the ovarian response to gonadotrophin stimulation in assisted reproduction patients who are considered to be poor responders. DESIGN: Prospective study. SETTING: Fertility unit. SAMPLE: Blood samples were collected on day five or six in the early follicular phase of an untreated menstrual cycle. Samples were collected from 69 patients. METHODS: Serum samples were assayed for FSH, AMH and inhibin B using commercial immunoassay kits. MAIN OUTCOME MEASURES: Response to gonadotrophin stimulation and number of eggs collected. RESULTS: Among the 69 patients, 52 patients completed an IVF cycle and 17 patients had to cancel the cycle because of poor ovarian response to gonadotrophin stimulation. Mean FSH levels were significantly higher (P < 0.05) in the cancelled group (10.69 +/- 2.27 mIU/mL) compared with the cycle-completed group (7.89 +/- 0.78 mIU/mL). Mean AMH levels were significantly lower (P < 0.01) in the cancelled group (0.175 +/- 0.04 ng/mL) compared with the cycle-completed group (1.13 +/- 0.2 ng/mL). Mean inhibin B levels were significantly lower (P < 0.001) in the cancelled group (70 +/- 12.79 pg/mL) compared with the completed group (126.9 +/- 8.8 pg/mL). Predictive statistics show that AMH is the best single marker and that the combination of FSH, AMH and inhibin B is modestly better than the single marker. Linear regression analysis in the cycle completed patients shows that although FSH (r= 0.25, P < 0.05) and inhibin B (r= 0.35, P < 0.05) have a significant linear association with the number of eggs collected, AMH has the greatest association (r= 0.69, P < 0.001) with the number of eggs collected among the parameters measured. CONCLUSION: In this particular group of IVF patients, AMH is the best single marker of ovarian response to gonadotrophin stimulation. The combined markers modestly improved the prediction.     

Reproductive aging and variability in the ovarian antral follicle count: application in the clinical setting

OBJECTIVE: To determine the extent of intercycle and interobserver variability in antral follicle (AF) count and their impact on stimulation quality in IVF. DESIGN: Prospective evaluation of the impact on AF count of GnRH agonist down-regulation and interobserver variability. Retrospective evaluation of intercycle variability in AF count. SETTING: University ART clinic. PATIENT(S): Twenty subjects were used to evaluate the effect of GnRH agonist down-regulation upon AF count; six of whom were used to evaluate interobserver variability. Fifty patients experiencing two or three cycles of IVF within a 1-year interval. INTERVENTION(S): Transvaginal ultrasound exams before and after down-regulation with a GnRH agonist. Videotaped day-3 transvaginal ultrasound exams. MAIN OUTCOME MEASURE(S): [1] Intercycle and interobserver variability in antral follicle count. [2] Oocytes retrieved, peak estradiol, gonadotropin dose, duration of stimulation and cancellation rates. RESULT(S): There is moderate intercycle and interobserver variability in AF counts. GnRH agonist down-regulation does not significantly change AF count. In infertility patients undergoing IVF, paired analysis between the low- and high-AF count cycles did not show a difference in quality of stimulation or cycle cancellation rates. CONCLUSIONS: Within an individual patient, higher AF count in a given cycle was not predictive of better stimulation compared with the case of a lower count cycle.     

Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome

Cycle day 3 basal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured in 441 patients in 758 consecutive cycles to determine their predictive value for stimulation quality and pregnancy rates in vitro fertilization (IVF). Patients with low basal FSH levels (less than 15 mIU/ml) had higher pregnancy rates per attempt than those with moderate levels (15 to 24.9 mIU/ml), both of which were higher than those with high FSH levels (greater than 25 mIU/ml). Basal LH and E2 values did not improve the predictive value beyond that provided by FSH. Ongoing pregnancy rates per attempt in the low, moderate, and high FSH groups were 17.0%, 9.3%, and 3.6%, respectively (P less than 0.01). The three groups differed significantly in the percentage of patients having two ovaries, the mean number of follicles aspirated per retrieval, the mean number of preovulatory oocytes obtained, and peak E2 values (P less than 0.01). Cycle day 3 FSH levels are predictive of pregnancy outcome and stimulation characteristics in IVF, and may be useful in counseling patients.     

The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome

The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.     

Prediction of ovarian reserve based on day-3 serum follicle stimulating hormone concentrations during the pituitary suppression cycle using a gonadotropin releasing hormone agonist in patients undergoing in vitro fertilization-embryo transfer.

Satisfactory results following in vitro fertilization-embryo transfer (IVF-ET) treatments depend on retrieving an appropriate number of mature oocytes without causing the development of ovarian hyperstimulation syndrome (OHSS). The present study was carried out to investigate whether the ovarian reserve is predictable based on the day-3 serum concentration of follicle stimulating hormone (FSH) during the pituitary suppression cycle using a gonadotropin releasing hormone (GnRH) agonist (defined as day-3 FSH) in patients undergoing IVF-ET treatment. Day-3 FSH before the administration of gonadotropin was assessed in 72 IVF-ET cycles from 59 infertile women. The mean+/-SD of day-3 FSH, the total amount of FSH plus human menopausal gonadotropin (hMG) administered, and the total number of oocytes retrieved was 5.5+/-2.6 mIU/ml, 2834.2+/-1236.5 IU and 7.7+/-5.8, respectively. There were significant correlations between day-3 FSH and the total amount of FSH-hMG administered (p < 0.001), and day-3 FSH and total number of oocytes retrieved (p < 0.001). There was a significant difference of day-3 FSH between patients who subsequently conceived (4.4+/-1.3 mIU/ml) and those who did not conceive (6.1+/-2.9 mIU/ml) (p = 0.001). There was also a significant difference of day-3 FSH between patients who developed moderate or severe OHSS (4.5+/-1.2 mIU/ml) and those who did not (5.9+/-2.8 mIU/ml) (p = 0.003). Receiver-operator characteristic curve analysis showed that the significant cut-off point for day-3 FSH for predicting ovarian reserve was 5.25 mIU/ml. These findings indicate that day 3-FSH is usefulfor predicting ovarian reserve during the pituitary suppression cycle using a GnRH agonist in patients undergoing IVF-ET.     

Clinical usefulness of basal FSH as a prognostic factor in patients undergoing intracytoplasmic sperm injection

OBJECTIVE: To determine if basal serum follicle stimulating hormone (FSH) level could be a prognostic factor of the clinical outcome in intracytoplasmic sperm injection (ICSI) cycles in the couples with male factor infertility. MATERIALS AND METHODS: From December 1995 to March 1998, total 118 patients underwent in vitro fertilization and embryo transfer (IVF-ET) with ICSI due to male factor infertility were included in this study. Patients were allocated to the low basal FSH group (< 8.5 mIU/ml) and the high basal FSH group (> or = 8.5 mIU/ml). The basal levels of FSH were measured in the 3rd day of menstrual cycle preceding ovarian stimulation cycle in total IVF cycles by immunoradiometric assay (IRMA). Statistical analysis was performed using Student's t-test, Fisher's exact test, and chi 2 test as appropriate. Statistical significance was defined as p < 0.05. RESULTS: The total dose of exogeneous gonadotropin required in the high basal FSH group was significantly higher than that in the low basal FSH group. The numbers of retrieved oocytes and oocytes with grade I, II were significantly higher in the low basal FSH group. The clinical pregnancy rate per cycle in the low basal FSH group (16.2%) was significantly higher than that in the high basal FSH group (4.0%). CONCLUSION: These results suggested that the basal serum FSH levels could be predictive of pregnancy outcome and the results of controlled ovarian hyperstimulation (COH) in ICSI cycles.     

Inhibition of gonadotropin surge by a brief mid-cycle regimen of ethinyl estradiol and norethindrone: possible role in in vitro fertilization.

Various methods to prevent premature luteinizing hormone (LH) surge and improve cycle control during hyperstimulation for in vitro fertilization (IVF) are standard of care. The purpose of the present study was to determine the influence of a 5-day regimen of ethinyl estradiol (EE) and norethindrone (NET) on folliculogenesis, gonadotropin surge, and ovulation. In a prospective randomized and comparative study, ten patients were assigned to two groups. A combination of 50 micrograms of EE and 1 mg of NET was used in groups I and II from days 6 through 10, and days 8 through 12, respectively. Blood samples and transvaginal ultrasound imaging were carried out throughout a 28-day cycle. Follicular diameter, plasma levels of LH, follicle-stimulating hormone (FSH), estradiol and progesterone, and endometrial thickness were determined. No LH surge or ovulation was detected in any patient studied. Peak estradiol concentrations were not significantly different between the groups (152.04 +/- 107.1 pg/ml vs 162.1 +/- 56.1 pg/ml [mean +/- SD] for groups I and II, respectively). No differences were noted between the groups for serum concentrations of FSH (range: 2-9 mIU/ml) or LH (range: 2-10 mIU/ml) for any given cycle day. Mean follicular diameters were not different between groups I and II (20.5 +/- 8.1 mm2 vs 20.6 +/- 14.2 mm2). Ultrasound assessment of mid-cycle follicular growth revealed diameters ranging from 18.5 mm2 to 34.0 mm2. Endometrial thickness ranged from 8 to 10 mm. There was no evidence of ovulation on ultrasound examination and either persistence or gradual resolution of follicles through the luteal phase. Peak serum concentrations at mid-luteal phase were < or = 2 ng/ml. In this pilot study, the combination of EE and NET restricted to a 5-day course beginning on day 6 or 8 permitted folliculogenesis but effectively inhibited midcycle LH surge and ovulation. Such regimens may have a role in IVF cycles for prevention of premature LH surges, especially as stimulation regimens evolve toward decreased gonadotropin use for stimulation and strict FSH preparations with the potential need for less complete pituitary suppression.     

Role of periovulatory luteinizing hormone concentrations during assisted reproductive technology cycles stimulated exclusively with recombinant follicle-stimulating hormone

OBJECTIVE: To study the effect of endogenous luteinizing hormone (LH) concentration on fertilization, pregnancy, and early pregnancy loss rates. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university center. PATIENT(S): One hundred sixty-six normogonadotropic patients undergoing IVF. INTERVENTION(S): Luteal phase pituitary down-regulation and recombinant FSH (Gonal-F) were used for ovarian stimulation. The mean of 4-5 serum LH concentrations, from stimulation days 5-12, was computed for analysis. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and early pregnancy loss rates according to periovulatory levels of LH. RESULT(S): Data were analyzed by stratifying patients according to a mean periovulatory LH value of 3 mIU/mL. After controlling for confounding variables with logistic regression, results showed that the fertilization rate was significantly lower in patients with a periovulatory LH <3 mIU/mL versus > or = 3 mIU/mL (52% and 58%, respectively; P=.03). Pregnancy rates and spontaneous abortion rates were similar in both groups. There were seven biochemical pregnancies, all in patients with an LH <3 mIU/mL (P=.07). CONCLUSION(S): Low endogenous LH concentrations (<3 mIU/mL) in the late follicular phase of an IVF cycle are associated with significantly lower fertilization rates and a trend toward higher biochemical pregnancy rates. It may be of clinical benefit, when exclusively using r-hFSH in ART cycles, to add LH in the late follicular phase or to further reduce the dose of GnRH agonist.     

Predictive usefulness of cycle day 10 follicle-stimulating hormone level in a clomiphene citrate challenge test for in vitro fertilization outcome in women younger than 40 years of age

OBJECTIVE: To determine the usefulness of the day 10 FSH level of a clomiphene citrate challenge test in predicting IVF outcome in women younger than 40 years of age. DESIGN: Retrospective chart review. SETTING: Academic fertility center. PATIENT(S): Three hundred fifty-three women younger than 40 years of age undergoing 483 IVF cycles. MAIN OUTCOME MEASURE(S): Delivery rates. RESULT(S): An inverse relationship was observed between the likelihood of successful pregnancy and both cycle day 3 and cycle day 10 FSH levels. In women with a normal day 3 FSH level, elevated day 10 FSH levels predicted similarly poor IVF outcomes as for women with an abnormal day 3 FSH level. There was no specific threshold FSH level beyond which pregnancies failed to occur. Successful pregnancies were achieved with aggressive stimulation even in women with FSH levels greater than 20 mIU/mL. CONCLUSION(S): The clomiphene citrate challenge test (CCCT) correlates with IVF outcomes in women younger than 40 years of age. Stimulated day 10 FSH levels are strongly predictive of decreased IVF success even when day 3 FSH levels are normal. Results of the CCCT are useful for patient counseling before the IVF cycle and for choosing the optimal gonadotropin regimen.     

Evidence of gonadal and gonadotropin antibodies in women with a suboptimal ovarian response to exogenous gonadotropin

Failure to respond to human menopausal gonadotropin (hMG) with adequate ovarian stimulation is associated with a poor prognosis in subsequent cycles in women participating in an in vitro fertilization/embryo transfer program. Sera from 26 menstruating women (mean age 38 +/- 4.3 years) identified as "low responders" with either tubal or male factor infertility, mean baseline FSH values of 11 mIU/mL, and peak serum estradiol levels lower than 300 pg/mL were assessed for specific antibodies to human ovary and gonadotropins. Twenty-five infertile women with tubal or male factor infertility with a good response to hMG served as controls. Ninety-two percent of low responders had antibodies to FSH and 65% had antibodies to LH when assessed by enzyme-linked immunosorbent assay. Similarly, 77% of low responders had ovarian antibodies. No hepatic antibodies were found in the sera of low responders, indicating that the positivity was not a general interaction with cell components. None of the "good responders" had antibodies to gonadotropins or to ovarian or liver tissue. The significant differences in antibodies between the groups supports a possible immunologic cause for low ovarian stimulation response to gonadotropin.     

Follicular atresia associated with concurrent initiation of gonadotropin-releasing hormone agonist and follicle-stimulating hormone for oocyte recruitment

The ability of gonadotropin-releasing hormone agonist (GnRHa) to cause an initial stimulation of serum gonadotropins was used for follicular recruitment for in vitro fertilization (IVF) in 12 patients with a history of low estradiol (E2) response to conventional gonadotropin stimulation. Stimulation was initiated on cycle day 3 with concurrent administration of leuprolide (1 mg/day subcutaneously) and follicle stimulating hormone (FSH, 4 ampules/day intramuscularly). An 8-fold increase in basal serum luteinizing hormone (LH) and a 4-fold increase in basal serum FSH was seen on cycle day 4. Serum progesterone levels rose significantly by day 6. When compared to prior IVF attempts in these patients, the mean day of human chorionic gonadotropin administration and corresponding E2 levels were not significantly different. More atretic oocytes and fewer preovulatory oocytes were retrieved using GnRHa, and no increase was seen in total oocytes retrieved. One patient was canceled for poor E2 response, and one patient conceived, with a current viable pregnancy. It is concluded that concurrent initiation of leuprolide and FSH stimulation on cycle day 3 in patients with prior low response does not improve oocyte recruitment, and the high LH environment generated from initial stimulation of the agonist may be detrimental to normal oocyte development.     

A preliminary study on reduced dose (33 or 25 microg) gonadotropin-releasing hormone agonist long protocol for multifollicular ovarian stimulation in patients with high basal serum follicle-stimulating hormone levels undergoing in vitro fertilization-embryo transfer.

The aim of the present study was to evaluate the clinical efficacy of half-dose (50 mug) and further reduced dose (33 or 25 mug) gonadotropin-releasing hormone agonist (GnRH-a; triptorelin) long protocols for multifollicular ovarian stimulation (MFOS) for patients with high basal serum follicle-stimulating hormone (FSH) level undergoing in vitro fertilization and embryo transfer (IVF-ET). One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH (>10.0 mIU/ml) were included in this retrospective study. Study subjects were assigned to two groups: continuous half-dose GnRH-a long protocol (group A, n = 63) vs. further reduced dose GnRH-a long protocol (group B, n = 39) from half-dose at the start of GnRH-a to one-third or one-quarter dose after pituitary downregulation. Exogenous FSH or human menopausal gonadotropin was administered for MFOS in step-down mode, four or fewer embryos were transferred, and the outcomes of MFOS were compared between the two groups. Serum estradiol (E(2)) level on the day of human chorionic gonadotropin administration was significantly higher in group B (mean +/- standard deviation (SD): 1318.3 +/- 1120.4 vs. 2054.9 +/- 1773.5 pg/ml, p = 0.015). The number of transferable and good-quality embryos was also significantly higher in group B (mean +/- SD: 2.9 +/- 1.7 vs. 3.7 +/- 2.0, p = 0.027; 1.8 +/- 1.4 vs. 2.7 +/- 2.0, p = 0.020). No statistically significant difference in the outcomes was observed with respect to the dose of gonadotropins administered, the number of oocytes retrieved or the clinical pregnancy rate. In conclusion, GnRH-a long protocol with a reduced dose, tapered from the starting half-dose to a third or a quarter of the normal dose after pituitary suppression, may be beneficial for MFOS in IVF-ET patients with a high basal serum FSH level. A further prospective randomized controlled study on a larger scale is needed to confirm these findings.     

Predictive value of the FSH:LH ratio on follicular and luteal phase characteristics of the human menstrual cycle

A prospective study was designed to assess the predictive value of gonadotropin measurements obtained during the early follicular phase upon the hormonal characteristics of the subsequent cycle. The data obtained in 12 normal cycles were used to compute the mean and confidence interval (mean +/- 2 SEM) of the FSH:LH ratio, FSH and LH plasma levels. The limits of the confidence intervals for these different parameters were used to classify the patients. Data of 204 patients were analysed. Low FSH:LH ratios (less than 1.34) are associated with an increase in follicular phase length (+2.4 days), a lower ovulatory rate, but neither luteal phase length nor progesterone levels differ between these two groups. When patients are classified according to FSH levels, our results show that low FSH levels (less than 2.94 mIU/ml) are associated with longer follicular (+2.6 days) and shorter (-1.1 days) luteal phase lengths, but ovulatory rate and progesterone levels in the luteal phase of the ovulatory cycles are similar to those obtained in patients of the normal or high FSH group. High LH levels (greater than 3.15 mIU/ml) are associated with a decreased ovulation rate but follicular and luteal phase characteristics are similar to those obtained in patients in the normal or low LH group. In conclusion, low FSH: LH ratios and low FSH plasma levels measured in the early follicular phase of the cycle are associated with longer follicular phase lengths; but basal gonadotropin measurements have limited predictive value on luteal phase characteristics.     

Use of follicle-stimulating hormone test to predict poor response in in vitro fertilization

OBJECTIVE: Optimized ovarian stimulation protocols are required for the success of in vitro fertilization (IVF). The purpose of this study was to estimate whether the ovarian reserve test using exogenous follicle-stimulating hormone (FSH) could predict ovarian response in IVF. METHODS: This was a prospective observational study of 110 patients who underwent their first IVF cycle. The FSH test was administered as 150 IU of urinary FSH daily from day 3 to day 6 of the menstrual cycle preceding the IVF cycle for evaluation of the plasma estradiol level. Outcomes of IVF, including ovarian response, were analyzed. RESULTS: A negative correlation was observed between the duration of stimulation and the result of the FSH test (r = -.238, P = .014) and between the dose of FSH per retrieved mature oocyte (metaphase II oocyte) and the result of the FSH test (r = -.308, P < .001). In addition, our results showed that the result of the FSH test was significantly lower in poor responders defined by FSH of 400 IU/metaphase II oocyte or greater (207 +/- 149 compared with 293 +/- 174 pg/mL, P = .007). CONCLUSION: The FSH test can be a useful tool for determining the conditions of individualized clinical management plans and optimizing stimulation protocols in IVF.     

The effect of thyrotropin-releasing hormone stimulation on serum levels of gonadotropins in women during the follicular and luteal phases of the menstrual cycle

Thyrotropin-releasing hormone (TRH) can stimulate the secretion of adenohypophyseal thyroid-stimulating hormone and prolactin (PRL). The effect of TRH on gonadotropin secretion has not been well defined. This study investigated the effect of TRH administration on the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during the early follicular and midluteal phases of the menstrual cycle in five ovulatory, euthyroid, and normoprolactinemic women. Two hundred micrograms of TRH were administered intravenously on days 3 to 5 and on days 21 to 23 of the same cycle. LH and FSH were measured prior to and every 30 minutes for 2 hours following TRH injection. Ovulation was confirmed in all cycles by midluteal progesterone. All women had normal thyroid-stimulating hormone (TSH) and PRL responses to TRH stimulation in both cycle phases. Baseline and stimulated gonadotropin levels were analyzed by analysis of variance. Thirty minutes following TRH infusion, follicular and luteal levels of LH (mIU/ml, mean +/- standard error of the mean) significantly increased from 6.0 +/- 0.8 to 8.0 +/- 1.1 (P less than 0.005), and from 4.8 +/- 0.6 to 7.6 +/- 0.7 (P less than 0.005), respectively. Levels of FSH increased during both phases of the cycle, but the elevation was not statistically significant. These results suggest that TRH can stimulate gonadotrope secretion of LH, but not of FSH, in both the follicular and luteal phases of the cycle.     

Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization.

OBJECTIVE: To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. DESIGN: A prospective, randomized controlled trial. SETTING: Hospital-based IVF Unit. PATIENT(S): Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. INTERVENTION(S): In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. MAIN OUTCOME MEASURE(S): Ovarian stimulation patterns and IVF outcome. RESULT(S): A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). CONCLUSION(S): Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.     

Evaluation of semen and pituitary gonadotropin function in men with untreated Hodgkin's disease

The reproductive capacities of 35 patients with Hodgkin's disease were assessed before treatment by semen evaluation and determination of basal hypothalamic-hypophyseal function and after stimulation with gonadotropin-releasing hormone (GnRH). Sixty-five percent of the patients had asthenozoospermia, 46% had teratozoospermia, and 28% had oligozoospermia. Normal semen was more frequently seen in asymptomatic patients (7 of 18) than in symptomatic patients (2 of 15). All the patients had normal basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and significantly low testosterone (T) levels (P less than 0.01). The FSH response to 100 micrograms of GnRH was normal, but the LH responses were all significantly low, both as delta % (28.4% +/- 18.7% versus 52.4% +/- 25.3%, P less than 0.005) and as peak values (36.7 +/- 20.7 mIU/ml versus 59.4 +/- 26.4 mIU/ml, P less than 0.01). It is believed that abnormal semen is a specific symptom of Hodgkin's disease, secondary to functional insufficiency of the hypothalamic-hypophyseal axis, with a relative decrease in T production.     

GnRHa flare and IVF pregnancy rates.

OBJECTIVES: GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF 'poor responders'. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in 'poor responders'. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in 'poor responders'. METHODS: Seventy-three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age-matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. 'Poor responders' consisted of patients with peak E(2) less than 1000 pg/ml and/or less than five mature follicles with diameter >15 mm on the day of hCG administration. Student's t-test was used to analyze the data and the chi-squared test was used to compare fertilization and pregnancy rates. RESULTS: The flare protocol produced higher peak E(2) levels (1647+/-747 vs. 720+/-258 mIU/ml, P<0.05) and a larger number of mature follicles (5.8+/-2.2 vs. 4.0+/-1.0 P<0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P>0.05, NS). CONCLUSIONS: A comparison between the flare protocol group and the age-matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E(2) levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.