Low serum estradiol concentrations after five days of controlled ovarian hyperstimulation for in vitro fertilization are associated with poor outcome

OBJECTIVE: To evaluate the prognostic significance of low serum E2 concentrations in controlled ovarian hyperstimulation (COH) cycles for IVF. DESIGN: Retrospective study. SETTING: Assisted conception unit of a university hospital. PATIENT(S): One thousand four hundred and forty patients undergoing COH for IVF. INTERVENTION(S): COH, serum E2 measurement, ultrasonographic scanning of ovarian follicles, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Cancellation and pregnancy rates. RESULT(S): Patients were classified into four groups according to serum E2 levels on the sixth day of COH: group A (E2 level < 50 pg/mL [114 cycles]), group B (E2 level 51-100 pg/mL [189 cycles]), group C (E2 level 101-200 pg/mL [320 cycles]), and group D (E2 level >200 pg/mL [817 cycles]). Group A experienced the highest cancellation rates (65.1%) and lowest pregnancy rates (7.8%) despite requiring significantly more hMG ampules (47.8+/-1.7). The cancellation rate was higher (75.1%) and no pregnancy occurred in a subset of group A in whom COH was initiated with > or =3 ampules (225 IU) of gonadotropins. CONCLUSION(S): In COH cycles using luteal phase buserelin, low initial serum E2 concentrations are associated with poor outcome.     

Early pituitary desensitization and ovarian suppression with leuprolide acetate is associated with in vitro fertilization-embryo transfer success

OBJECTIVE: To determine if the timing of the onset of pituitary desensitization and ovarian suppression using follicular phase leuprolide acetate (LA) is associated with in vitro fertilization-embryo transfer (IVF-ET) success for pregnancy. DESIGN: Retrospective series of IVF patients undergoing pituitary desensitization and ovarian suppression before beginning controlled ovarian hyperstimulation for IVF-ET. SETTING: Tertiary infertility practice. PATIENTS: Seventy-eight women for 80 cycles began LA on day 1 of their menstrual cycle. After 11 days of LA, 47 (59%) cycles in group I had suppressed serum estradiol (E2) levels less than 40 pg/mL, in contrast to 33 (41%) cycles in group II not adequately suppressed, thereby requiring additional days to achieve suppression. INTERVENTIONS: Controlled ovarian hyperstimulation was started when patients were satisfactorily suppressed, i.e., E2 less than 40 pg/mL. MAIN OUTCOME MEASURE(S): Mean E2 response, ampules of human menopausal gonadotropin, cancellation rates, number of oocytes retrieved, fertilization rates, and pregnancy rates (PRs) per cycle were examined between groups I and II. RESULTS: Group I demonstrated a greater mean E2 response on the day of human chorionic gonadotropin 1,735 pg/mL versus 1,470 pg/mL (P = 0.008), a greater fertilization rate 64% versus 55% (P = 0.02), and a higher PR per cycle 34% versus 12% (P = 0.036) compared with group II. CONCLUSIONS: Women who achieved desensitization-suppression within 11 days of initiating LA demonstrated a more favorable outcome for IVF-ET than those who did not.     

Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-midluteal estradiol levels in IVF cycles

Purpose : To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. Methods : The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (<100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. Results : Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100–500 pg/mL) and high (>500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). Conclusions : hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.     

Predictive value of mid luteal progesterone concentration before luteal support in controlled ovarian hyperstimulation with intrauterine insemination

BACKGROUND: There is no published data assessing whether higher mid luteal serum progesterone (P4) levels are associated with a higher cycle pregnancy rate (CPR) in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI). Aims: To assess whether the mid luteal serum P4 level is predictive of pregnancy in COH with IUI. METHODS: A retrospective cohort study of all women with unexplained, minimal endometriosis or mild male factor infertility who underwent COH with IUI between October 1999 and December 2000 at our department was analysed. The COH was achieved with follicle stimulating hormone injections. All cycles were triggered with human chorionic gonadotropin when at least one follicle > or =15 mm was visible on ultrasound and IUI performed the following day. A serum P4 and beta human chorionic gonadotropin level was measured at 7 and 14 days post-trigger, respectively. RESULTS: There were 33 pregnancies in the 188 cycles analysed, giving a CPR of 18%. The median (range) mid luteal P4 level for all cycles was 51 nmol/L (1.8-234). This did not differ between the pregnant (55 nmol/L) and non-pregnant (50 nmol/L) cycles (P=0.282, Mann-Whitney U-test). There was also no difference in CPR between cohorts below or above the cut-off levels of 33 nmol/L (25th percentile) (13.3 vs 18.9%; P=0.39), 51 nmol/L (50th percentile) (16.0 vs 19.1%; P=0.57), or 69 nmol/L (75th percentile) (16.3 vs 21.3%; P=0.44), respectively. CONCLUSIONS: Increased mid luteal serum P4 levels are not associated with a higher CPR in women undergoing COH with IUI. However, a low mid luteal P4 level < or =25 nmol/L may help predict treatment failure.     

不同黄体支持方法对体外受精-胚胎移植结果的影响

目的:探讨三种黄体支持方法对体外受精-胚胎移植(IVF-ET)结果的影响。方法:回顾性分析195个IVF-ET周期的结果,根据注射hCG当天的血E2水平、B超示直径≥14 mm卵泡数目及所用的黄体支持方法分组。A组:112例,E2<2 000 pg/mL,直径≥14 mm的卵泡数<10个,hCG进行黄体支持;对E2≥2 000 pg/mL,卵泡数目≥10个者,随机分为两组,B组,46例,单用黄体酮进行黄体支持;C组,37例,黄体酮加雌激素进行黄体支持。结果: 三组间妊娠率、种植率、流产率、OHSS发生率差异均无显著性,P>0.05。结论:hCG用于IVF黄体支持并不优于黄体酮,但在一定程度上可避免某些患者由于注射黄体酮产生的痛苦。黄体酮+雌激素进行黄体支持应该是黄体支持较合理的方案,还需进一步研究。     

Controlled ovarian hyperstimulation. Relationship of early serum E2 levels to the ultimate response of oocyte donors

OBJECTIVE: To assess the predictive value of measuring serum day 5 E2 and in vitro fertilization (IVF) cycle outcome of oocyte donors undergoing controlled ovarian hyperstimulation (COH). STUDY DESIGN: Retrospective data analysis. RESULTS: Day 5 E2 significantly correlated with the peak serum E2 and number of retrieved mature oocytes. The pregnancy rates associated with stimulated day 5 E2 > 70 pg/mL were significantly greater than in cycles with levels < 70 pg/mL (58%, 71/123, versus 25%, 15/60; P < .05). CONCLUSION: The cycle performance of an oocyte donor can be predicted by measuring cycle day 5 serum E2 during COH. Poor-prognosis cycles can be identified and discontinued, saving patients and the program unnecessary exspense.     

The influence of estradiol/follicle and estradiol/oocyte ratios on the outcome of controlled ovarian stimulation for in vitro fertilization.

OBJECTIVE: The aim of the study was to evaluate the influence of the ratios of estradiol (E2) to either the number of follicles >14 mm on the day of human chorionic gonadotropin administration (E2/follicle) or the number of oocytes retrieved (E2/oocytes) during controlled ovarian hyperstimulation (COH) with gonadotropin-releasing hormone (GnRH)-agonist (agonist group) and GnRH-antagonist (antagonist group), on the outcome of in vitro fertilization (IVF) cycles. PATIENTS AND METHODS: All consecutive women aged <35 years admitted to our IVF unit during a 6-year period with normal to high response to COH were retrospectively studied. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred and pregnancy rate were assessed. RESULTS: Six hundred and ninety consecutive IVF cycles were evaluated, 301 in the agonist group and 389 in the antagonist group. The ratios of E2/follicle and E2/oocyte were significantly higher in the agonist group (p < 0.001 for both). Moreover, while pregnancy rates within E2/oocyte ratio of 100-200 pg/ml were comparable between the agonist and antagonist groups, when E2/oocyte ratios were <100 pg/ml or >200 pg/ml, pregnancy rates were significantly higher in the agonist group. Furthermore, no difference in pregnancy rates was observed within the agonist group between different E2/oocytes ratios, while within the antagonist group, higher pregnancy rates were observed when comparing those with E2/oocyte ratio of 100-200 pg/ml with those with E2/oocyte ratio <100 pg/ml or >200 pg/ml. CONCLUSION: While E2/oocyte ratio cannot predict the success of GnRH-agonist protocol, patients undergoing GnRH-antagonist protocol should reach E2/oocyte ratio within the 100-200 pg/ml range in order to achieve the best IVF outcome.     

Progesterone levels on the day of human chorionic gonadotropin administration in cycles with gonadotropin-releasing hormone agonist suppression are not predictive of pregnancy outcome

In in vitro fertilization (IVF) cycles using gonadotropin-releasing hormone agonist (GnRH-a) suppression, we investigated whether an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration indicates premature luteinization and is associated with a lower pregnancy rate. We retrospectively studied 101 patients treated with the GnRH-a leuprolide acetate, begun in the luteal phase of the prior menstrual cycle and continued until the day of hCG administration. On the day of hCG, 72 patients had P less than 0.9 ng/mL and 29 had less than or equal to 0.9 ng/mL. Patients in the high P group had a significantly greater estradiol level on the day of hCG. No significant difference in clinical pregnancy rates or ongoing pregnancy rates occurred between the low P and high P groups. We conclude that in IVF cycles pretreated with GnRH-a, P levels on the day of hCG are not predictive of conceiving in that cycle.     

黄体期个体化雌激素补充方案对IVF-ET治疗结局的影响

目的:探讨黄体期个体化添加不同剂量雌激素对体外受精-胚胎移植(IVF-ET)胚胎种植率和临床妊娠率的影响。方法:回顾性分析104个长方案控制性促排卵(COH)IVF-ET周期,根据其移植日血清E2水平下降幅度分为4组,A组:E2下降<30%,12个周期,单用黄体酮进行黄体期支持;B组:E2下降30%-39%,18个周期,黄体期支持采用黄体酮+3mg/d雌激素;C组:E2下降40%-49%,16个周期,D组:E2下降≥50%,58个周期,C组、D组患者黄体期支持采用黄体酮+4mg/d雌激素。结果:各组的取卵数目、受精率、卵裂率、优质胚胎数、内膜厚度和移植胚胎数相比差异均无显著性(P>0.05)。A组、B组、C组间胚胎种植率和临床妊娠率无统计学差异;而D组与其余3组比,胚胎种植率和临床妊娠率显著下降(P<0.05)。结论:①在长方案COH的IVF-ET中,当移植日血清E2水平下降幅度≥30%时黄体期支持补充雌激素可以改善胚胎种植率和临床妊娠率;②E2下降幅度大的患者可能需要增加雌激素的添加剂量。     

Goserelin Acetate (Zoladex)with or without Hormone Replacement Therapy for the Treatment of Endometriosis

Objective: To determine if women undergoing GnRH agonist-hMG stimulated IVF cycles can undergo successful discontinuation of luteal phase support.

Design: A protocol for selective discontinuation of luteal phase support was evaluated prospectively in women undergoing assisted reproduction cycles.

Setting: A tertiary care institutional-based assisted reproduction program.

Patient(s): One hundred eighty-eight women who conceived after an IVF or zygote intrafallopian transfer cycle including a GnRH agonist between January 1994 and June 1997.

Intervention(s): Women with serum progesterone levels of ≥60 ng/mL at 4 weeks’ gestation were selected for discontinuation of their luteal phase support.

Main Outcome Measure(s): Delivery rate.

Result(s): Sixty-three women (62.4%) met the criteria for discontinuation of luteal phase support. There were no differences in the mean age, peak E₂ levels, number of follicles, number of embryos transferred, or delivery rates (85.7% versus 78.9%) between the women who did and those who did not have discontinuation of their progesterone supplementation.

Conclusion(s): These data reveal that luteal phase support can be discontinued successfully for selective women undergoing IVF who are receiving a GnRH agonist.     

Effects of ovarian high response on implantation and pregnancy outcome during controlled ovarian hyperstimulation (with GnRH agonist and rFSH)

BACKGROUND: The study was aimed at investigating the effects of ovarian high response during controlled ovarian hyperstimulation (COH) on implantation and pregnancy outcome in fresh IVF/ICSI cycles, and subsequent frozen-thawed embryo transfer (FET) cycles. METHODS: An analysis of 1,196 cycles using a long protocol with GnRHa and rFSH was performed. A serum oestrial level (peak E(2)) was obtained on the day of hCG administration, and patients were grouped by peak E(2) percentile distribution into 3 groups. Normal responder was set as cut-off concentrations between percentile (P)25 and P75 (Group A: 1,199-3,047 pg/ml, 595 cycles). Moderate high responders were classified as peak E(2) between P75-P90 (Group B: 3,048-4,127 pg/ml, 180 cycles). For the high response group, the E(2) cut-off concentration was set as P90 and above (Group C: >or=4,128 pg/ml, 119 cycles). Oocyte/embryo parameters and clinical outcomes were compared among the 3 groups in fresh cycles and subsequent FET cycles. RESULTS: Comparisons between groups revealed no difference in the quality of oocyte retrieved and in fertilisation rates. Group C showed decreased trends in implantation and pregnancy rates compared with Group A, but statistical significance was reached only for the difference in implantation rates. Implantation and pregnancy rates in FET cycles were similar among the 3 groups. CONCLUSIONS: High serum estrogen levels were detrimental to implantation, but not to the quality of oocytes, which may be due to an adverse effect on endometrial receptivity in COH cycles.     

Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists

OBJECTIVE: To evaluate the endometrium obtained during the luteal phase of controlled ovarian hyperstimulation (COH) cycles utilizing gonadotropin-releasing hormone (GnRH) antagonists, and to compare these findings with those obtained in cycles utilizing a GnRH agonist and with artificial cycles among recipients. DESIGN: Prospective evaluation of oocyte donors. SETTING: University-based in vitro fertilization (IVF) center. PATIENT(S): Fifteen oocyte donors undergoing standard COH were enrolled in 1 of 3 COH groups, and 40 recipients of oocyte donation were used as a control group. INTERVENTION(S): Controlled ovarian hyperstimulation and endometrial biopsy. MAIN OUTCOME MEASURE(S): Histological dating of endometrial biopsies, serum estradiol (E(2)) and progesterone levels. RESULT(S): On the day of oocyte retrieval, endometrial maturation was advanced by an average of 5.8 +/- 0.4 days in the antagonist group and 5.9 +/- 0.7 days in the agonist group. This advancement persisted on day 7 postoocyte retrieval. Serum progesterone levels were elevated before human chorionic gonadotropin (hCG) administration, but remained similar in both groups. CONCLUSION(S): Controlled ovarian hyperstimulation is associated with elevated progesterone levels in the late follicular phase and accelerated endometrial maturation in the subsequent luteal phase. No significant differences exist between preretrieval serial serum progesterone levels and luteal phase endometrial histology between cycles utilizing GnRH agonists or antagonists.     

Prospective randomized comparison of human chorionic gonadotropin versus intramuscular progesterone for luteal-phase support in assisted reproduction

Objective The purpose of the study was to determine the impact of two forms of luteal-phase supplementation, human chorionic gonadotropin (hCG) and progesterone (P), during gonadotropin releasing hormone agonist (GnRha)/controlled ovarian hyperstimulation (COH) cycles.Design and Patients The study was a prospective, randomized evaluation of 77 patients. Group 1 patients (n=38) received 2000 IU of hCG, injected subcutaneously, on days 3, 6, 9, and 12 after transvaginal aspiration of the oocytes (TVA=day 0). Group 2 patients (n=39) received 50-mg daily injections of intramuscular (i.m.) P from days 2 to 14 after TVA. Blood tests were performed on days 0, 5, 8, and 12 after TVA.Setting The in vitro fertilization program of a tertiary care institution was the study setting.Main Outcome Measures The main outcome measures were (1) pregnancy and implantation rates; (2) serum estradiol (E), P, and hCG levels; and (3) occurrence of side effects.Results Clinical pregnancy and implantation rates in group 1 versus group 2 were similar (36.7 vs 35.3 and 12 vs 14%, respectively). Regardless of pregnancy occurrence, on days 8 and 12 after TVA, serum E and P levels were higher in group 1 than group 2 but the resulting E/P ratios were similar. Five of 38 patients (group 1) developed moderate to severe ovarian hyperstimulation syndrome (OHSS) right after the first or second supplementary hCG injection. In these patients, the mean serum E level on the day of hCG trigger injection was about 3250 pg/ml and the number of follicles was between 9 and 17. In 6 of 39 patients (group 2) allergic reactions were observed at the P injection sites.Conclusions Based on our data, hCG administration as a form of luteal supplementation did not translate, in comparison to P, into significant benefits for the patients. At the same time, it significantly increased the risk of ovarian hyperstimulation. We suggest that whenever, during COH cycles, serum E levels are over 2500 pg/ml and the number of follicles exceeds 10, luteal support with hCG should be excluded.Presented at the 41st Annual Meeting of the Pacific Coast Fertility Society, Indian Wells, California, April 14–18, 1993.     

Luteal phase hormonal profile in prediction of pregnancy outcome after assisted reproduction

The clinical efficacy of luteal phase hormones including estradiol and progesterone in the prediction of pregnancy and its outcome in ICSI-ET cycles was evaluated. In 121 ICSI-ET cycles, serial estradiol and progesterone levels were measured in the luteal phase. The day of ovum pick-up was designated as day 0. All the patients had luteal support with vaginal progesterone suppositories after embryo transfer (ET). Serial estradiol measurements were performed on days 8, 11 and 13 and progesterone level on day 11. A single dose of hCG was given for corpus luteum rescue 5000 IU, if day 8 estradiol level <200pg/ml; 2000IU, if estradiol between 200 and 800pg/ml; no hCG if estradiol level >800pg/ml). On day 15, beta-hCG level was measured to detect pregnancy and if positive, injected on day 17. Fifty-seven pregnancies were achieved in 121 cases after ET (47%). Clinical pregnancy rate and ongoing pregnancy rate per ET were 37.1 and 30%, respectively. While there was no difference between progesterone levels measured on day 11, estradiol levels on days 11 and 13 were significantly higher in women who became pregnant. In 40 patients taking only progesterone and in 81 cases taking hCG plus progesterone, estradiol levels on days 11 and 13 were significantly higher in women who became pregnant. Progesterone levels on day 11, in progesterone treated groups, did not differ between pregnant and non-pregnant patients. Estradiol and progesterone levels on day 11 and estradiol levels on day 13 showed a big overlap between pregnant and non-pregnant patients. The efficacy of serial testing was evaluated. An increase in estradiol level from day 11 to 13 was associated with 71% pregnancy rate (72% ongoing). In the case of a decrease in estradiol level, the pregnancy rate was 18% of which 80% had to implant. Rising estradiol in the late luteal phase is associated with higher pregnancy rate and more successful pregnancy outcome.     

Comparison of a single half-dose, long-acting form of gonadotropin-releasing hormone analog (GnRH-a) and a short-acting form of GnRH-a for pituitary suppression in a controlled ovarian hyperstimulation program

OBJECTIVE: To compare the effect of a single low-dose leuprolide acetate depot (LA depot) and leuprolide acetate (LA) on pituitary down-regulation in women undergoing controlled ovarian hyperstimulation (COH). DESIGN: Retrospective study.Setting: An IVF unit of an academic medical center. PATIENT(s): Women who underwent COH and IVF-ET. INTERVENTION(s): Pituitary down-regulation with half-dose LA depot (1.88 mg sc, group 1) or LA (0.5 mg/d sc, group 2) was started on menstrual days 21-23. MAIN OUTCOME MEASURE(s): The concentrations of estradiol (E(2)), FSH, LH, gonadotropin dosages, the numbers of oocytes retrieved, oocytes fertilized and embryos transferred, and pregnancy rates of the two groups were compared. RESULT(s): A total of 289 patients in group 1 and 158 in group 2 were included. There were no statistically significant differences between the two groups in baseline concentrations of E(2) and FSH, concentrations of E(2), FSH, and LH during hCG administration, gonadotropin dosage, the number of oocytes retrieved, the number of oocytes fertilized and embryos transferred, and pregnancy rates. CONCLUSION(s): Single half-dose LA depot offers a useful alternative for pituitary suppression in ovarian stimulation for IVF.     

Serum anti-Mullerian hormone levels correlate with ovarian response in idiopathic hypogonadotropic hypogonadism

Purpose

The role of serum AMH levels in prediction of ovarian response in idiopathic hypogonadotropic hypogonadism (IHH) was evaluated.

Material method(s)

Twelve patients with IHH underwent controlled ovarian hyperstimulation (COH) for IVF were enrolled in this prospective study. Serum AMH levels were studied on the 2nd or 3rd day of an induced menstrual cycle by a preceding low-dose oral contraceptive pill treatment. A fixed dose (150–300 IU/day) of hMG was given in all COH cycles. Correlations between serum AMH levels, COH outcomes and embryological data were investigated.

Results

Mean serum AMH levels was 3.47 ± 2.15 ng/mL and mean serum peak estradiol was 2196 ± 1705 pg/mL. Mean number of follicles >14 mm, >17 mm on hCG day and MII oocytes were 4.14 ± 3.2, 4 ± 2.5 and 7.28 ± 3.5, respectively. Mean number of grade A embryos and transferred embryos were 3.28 ± 2.4 and 2.5 ± 0.7, respectively. The clinical pregnancy rate per patient was 41.6 % (5/12). Positive correlations were observed between serum AMH levels and MII oocytes (r = 0.84), grade A embryos (r = 0.85), serum peak estradiol levels (r = 0.87), and number of follicles >14 mm (r = 0.83) and >17 mm (r = 0.81) on hCG day, respectively.

Conclusion

AMH appears as a promising marker of ovarian response in patients with IHH undergoing IVF.     

Elevated E2: oocyte ratio in women undergoing IVF and tubal ET. Correlation with a decrease in the implantation rate

OBJECTIVE: To investigate the influence of various estradiol (E2): oocyte ratios on reproductive outcome in women undergoing in vitro fertilization and tubal embryo transfer (IVF-TET). STUDY DESIGN: Two hundred seven women undergoing 251 IVF-TET cycles were recruited in this retrospective study. All the women received a flare-up gonadotropin releasing hormone agonist (GnRHa) protocol to achieve ovarian hyperstimulation. Oocyte retrieval was performed 34-36 hours after human chorionic gonadotropin (hCG) injection, followed by TET two days later. RESULTS: An E2: oocyte ratio > or = 350 pg/mL had a higher E2 level (2,213 +/- 2,258 vs. 1,553 +/- 972 pg/mL, P < .05) and fertilization rate (77 +/- 23 vs. 64 +/- 23%, P < .001) but a lower oocyte number (4.8 +/- 4.7 vs. 7.6 +/- 4.8, P < .001) than in those with a ratio < 350 pg/mL. The pregnancy (17.9% vs. 32.8%, P = .03) and implantation (5.3% vs. 12.9%, P = .008) rates were significantly decreased in cycles with an E2: oocyte ratio > or = 350 pg/mL as compared to those with a ratio < 350 pg/mL. CONCLUSION: IVF-TET cycles with an elevated E2: oocyte ratio correlated with lower pregnancy and implantation rates. The poor reproductive outcome possibly was due to the relatively high E2 concentration, which might have a detrimental effect on endometrial receptivity.     

Serum progesterone concentration on day of embryo transfer in donor oocyte cycles

Purpose

To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles.

Methods

Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included (n = 229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50–100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50–100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (> = 24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age.

Results

Mean recipient serum P at ET was 25.5 ± 10.1 ng/mL. Recipients with P < 20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR = 0.75, 95 % CI = 0.60–0.94, p = 0.01) and live birth (RR = 0.77, 95 % CI = 0.60–0.98, p = 0.04), as compared to those with P ≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients.

Conclusions

Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.     

Endogenous LH Surge Versus hCG as Ovulation Trigger After Low-Dose Highly Purified FSH in IUI: A Comparison of 761 Cycles

Purpose: The results obtained with a protocol consisting of ovarian stimulation with low doses of highly purified FSH (FSH HP), administration of a GnRH analogue to induce an endogenous surge of gonadotropins, and IUI were evaluated. These results were compared with those seen with similar FSH stimulation and hCG administration followed by IUI. Methods: Three hundred sixty-four patients scheduled for IUI, after inclusion in a total of 345 FSH HP/GnRH-stimulated cycles and 416 FSH HP/HCG-stimulated cycles, were studied. The stimulation protocol consisted of daily subcutaneous injection of 75 IU of FSH HP from day 3 or 5 of the cycle, depending on the duration of the spontaneous cycle. hCG was administered on days 0, +2, and +5 to support the luteal phase. Monitoring was conducted using circulating estradiol levels and vaginal ultrasonography. Administration of two s.c. doses of leuprolide acetate (LA) or 7500 IU of i.m. hCG when at least one 18-mm-diameter follicle was seen and estradiol levels reached 120 pg/ml per follicle with a diameter 16 mm. Intrauterine insemination was with semen capacitated by swim-up, thawed at room temperature if previously frozen. Results: The ovulation rate was 99.28 after hCG and 99.23 with LA. No significant differences were seen between the estradiol and progesterone levels of both groups or in the estradiol/progesterone ratio. The duration of the luteal phase was similar in both groups. Pregnancy rates per cycle were 17.31% (hCG) and 27.25% (LA), respectively (P = 0.0007), and abortion rates 22.22% (hCG) and 24.47% (LA), respectively. No cases of ovarian hyperstimulation were seen. Conclusions: After FSH HP administration according to a low-dose protocol, the use of LA to trigger a gonadotropin surge as a means of inducing ovulation in FSH-stimulated women could be a good alternative to improve the results and prevent ovarian hyperstimulation in IUI cycles.     

Serum estradiol levels after 4 days of ovarian hyperstimulation in oocyte donors are predictive of embryo quality and clinical outcomes

OBJECTIVE: To determine whether estradiol (E(2)) levels after 4 days of ovarian hyperstimulation in leuprolide-downregulated cycles are predictive of embryo quality and pregnancy outcome in oocyte donation. MATERIAL AND METHODS: Retrospective analysis of 287 consecutive oocyte donation cycles performed at a university assisted reproduction therapy program between January 1996 and December 2000. Oocyte donors and recipients followed a non-varied standard synchronization regimen. A serum E(2) (day-5 E(2)) was obtained from egg donors the morning after leuprolide acetate downregulation and 4 days after hMG/FSH administration. Day-5 E(2) was categorized into 3 groups: group I <75 pg/ml; group II 75-350 pg/ml, and group III > or =350 pg/ml. All embryo transfers were performed 3 days after oocyte recovery. RESULTS: Elevated day-5 E(2) levels were directly correlated with higher average embryo scores, greater number of oocytes retrieved, and greater number of embryos available for transfer and cryopreservation. Improved pregnancy outcomes were also noted for group III (day-5 E(2) level >350 pg/ml). CONCLUSION: After 4 days of gonadotropin stimulation, an E(2) level of >350 pg/ml is most predictive of higher embryo grade and pregnancy outcome in oocyte donation.