Substituting human chorionic gonadotropin by gonadotropin-releasing hormone agonist to trigger final follicular maturation,during controlled ovarian hyperstimulation,results in less systemic inflammation

Background.?To investigate the degree of systemic inflammation, as reflected by serum C-reactive protein (CRP) levels, associated with controlled ovarian hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist for the induction of final follicular maturation.

Design.?Prospective, observational study.

Setting.?An in vitro fertilization (IVF) unit of an academic medical center.

Patients.?Twenty-four women undergoing COH and IVF with the flexible GnRH antagonist protocol were prospectively assigned to receive hCG or GnRH agonist for the induction of final follicular maturation.

Methods.?Blood was drawn three times during COH for measurement of sex-steroid and CRP levels: the day on which adequate suppression was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time points in the two groups.

Results.?No between-group differences were observed in terms of patient age, gonadotropin dosage, duration of stimulation or number of oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0, but the difference was significant only in the hCG group (p<0.03 for both). The percentage change in CRP levels after hCG administration (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%).

Conclusion.?Administration of GnRH agonist in patients undergoing COH for IVF yields a lesser degree of systemic inflammation, as reflected by CRP levels, than hCG.     

Controlled ovarian hyperstimulation using multi-dose gonadotropin-releasing hormone (GnRH) antagonist results in less systemic inflammation than the GnRH-agonist long protocol

Objective. The aim of the study was to investigate whether controlled ovarian hyperstimulation (COH) using multi-dose gonadotropin-releasing hormone (GnRH) antagonist results in a lesser degree of systemic inflammation than the GnRH-agonist long protocol.

Design. Prospective, observational study.

Patients and methods. Blood was drawn three times during the COH cycle from patients undergoing the long GnRH-agonist protocol (agonist group) (n = 12) or the multi-dose GnRH-antagonist protocol (antagonist group) (n = 15): the day on which adequate suppression was obtained (agonist group), or day 2 or 3 of the menstrual cycle and before gonadotropin treatment (antagonist group) (Day-0); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum C-reactive protein (CRP) were compared between the two study groups among the three time points.

Results. While no between-group differences were observed in patient age or ovarian stimulation characteristics, a significantly higher number of oocytes were retrieved in the antagonist compared with the agonist group. In both groups, serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0. While serum CRP levels were higher on Day-hCG than Day-0, the difference was statistically significant only for the agonist group (p < 0.05). Moreover, Day-OPU serum CRP levels were significantly higher in the agonist than in the antagonist subgroup.

Conclusion. COH using the multi-dose GnRH-antagonist protocol yields a lesser degree of systemic inflammation, as reflected by CRP levels, than the GnRH-agonist long protocol.     

Ovarian androgens but not estrogens correlate with the degree of systemic inflammation observed during controlled ovarian hyperstimulation.

AIM: To investigate the behavior and association of serum androgen and serum C-reactive protein (CRP) in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Prospective, observational study.Setting. An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 15 patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum CRP were compared among the three time points. RESULTS: There was a significant increase in serum ovarian androgen levels during gonadotropin treatment. After hCG administration, there was a significant increase in the levels of both serum CRP and ovarian androgens (testosterone, androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone). Significant correlations were observed between CRP and ovarian androgen levels but not with dehydroepiandrosterone sulfate or estradiol levels. CONCLUSION: In patients undergoing COH for IVF, ovarian androgen levels increase in correlation with the degree of inflammation, as reflected by CRP levels. Further studies are necessary to elucidate whether androgens play a role in or are predictive of the systemic inflammatory response in COH.     

Soluble L-selectin levels during controlled ovarian hyperstimulation.

We sought to determine whether neutrophil activation, as reflected by soluble L-selectin levels, plays a role in controlled ovarian hyperstimulation (COH) and the possible correlation between soluble L-selectin and serum sex steroid levels. The study population consisted of 14 consecutive patients undergoing our routine in vitro fertilization (IVF) long gonadotropin-releasing hormone (GnRH) analog protocol. Blood was drawn three times during the COH cycle: (1) on the day when adequate suppression was obtained (Day-S); (2) on the day of, or the day prior to, human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) on the day of ovum pick-up (Day-OPU). Levels of sex steroids and plasma soluble leukocyte selectin (L-selectin) were compared among the three time points. Soluble L-selectin was measured with a commercial sandwich enzyme-linked immunosorbent assay (ELISA). The results showed significantly higher levels of soluble L-selectin on Day-OPU than on Day-S and Day-hCG, and significantly lower levels on Day-hCG than Day-S. Though no significant correlations were found between soluble L-selectin and serum estradiol or hCG levels, soluble L-selectin positively correlated with serum progesterone levels. We conclude that hCG administration leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for predicting and preventing complications of COH.     

Serum and follicular fluid leptin levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycle

OBJECTIVE: To determine serum and follicular fluid leptin levels in patients undergoing controlled ovarian hyperstimulation (COH) for an in vitro fertilization-embryo transfer (IVF-ET) cycle and their possible correlation to COH variables. Setting: Large university-based IVF unit. Patients: 16 consecutive patients undergoing our routine IVF long gonadotrophin-releasing hormone-analog protocol. INTERVENTIONS AIND MAIN OUTCOME MEASURES: Blood was drawn three times during the COH cycle: 1) day on which adequate suppression was obtained (Day-S); 2) day of or prior to human chorionic gonadotrophin (hCG) administration (Day-hCG); and 3) day of ovum pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid leptin were compared among the three time points. Serum leptin was measured with a commercial two-site immunoradiometric assay. RESULTS: Results showed significantly higher levels of serum leptin on Day-OPU and Day-hCG than on Day-S, and significantly higher follicular than serum leptin levels on Day-OPU. Though a significant correlation was observed between serum leptin and body mass index (BMI), no correlations were found between serum or follicular fluid leptin and serum sex-steroid levels or IVF treatment variables. CONCLUSION: While serum leptin increases during COH for IVF, there is apparently no correlation of serum and follicular leptin levels with sex-steroid levels or IVF outcome.     

Serum androgen levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycles.

AIM: To investigate androgen behavior during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: A prospective, observational study. SETTING: An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 17 consecutive patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). RESULTS: There was a significant increase in serum sex steroid levels during gonadotropin treatment. After hCG administration, there was a significant increase in levels of serum 17-hydroxyprogesterone (17-OHP) and ovarian androgens (total and free testosterone and androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone sulfate). Significant correlations were observed between plasma estradiol (E(2)) and androgen levels during COH and until hCG administration, but not after hCG administration. The E(2)/testosterone ratio increased significantly during COH and until hCG administration, and then decreased significantly. The number of oocytes retrieved correlated significantly with serum 17-OHP, E(2) and E(2)/testosterone ratio. The number of gonadotropin ampoules used correlated inversely only with serum E(2) levels. CONCLUSION: In patients undergoing COH for IVF, androgen levels increase in response to gonadotropin, and then again after hCG administration. Although the E(2)/testosterone ratio correlates with the number of oocytes retrieved, androgen levels do not.     

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.     

Subtle progesterone rise in the single-dose gonadotropin-releasing hormone antagonist (cetrorelix) stimulation protocol in patients undergoing in vitro fertilization or intracytoplasmic sperm injection cycles.

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P < 1.2 ng/ml or P >/= 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P >/= 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p < 0.001) on the day of hCG injection than the group with P < 1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.     

1000IU hCG在控制性卵巢刺激过程中诱发卵泡成熟作用的初步研究

目的:评估1 000 IU低剂量hCG在控制性卵巢刺激(COS)过程中诱发卵泡成熟的作用。方法:35例接受IVF/ICSI-ET治疗的患者进行35个周期的COS。在诱发卵泡成熟日,肌肉注射hCG1 000 IU;并按照血E2水平分为卵巢正常反应组(E2<3 000 pg/ml,A组,12例)和卵巢高反应组(E2≥3 000 pg/ml,B组,23例),统计分析IVF/ICSI-ET结局。结果:35例患者均获得成熟卵母细胞并进行了胚胎移植,平均获卵数为13.5±7.7枚,平均成熟卵母细胞数为11.6±6.7枚,平均受精卵数为10.8±5.6枚,平均胚胎数为10.0±5.6枚,平均移植胚胎数1.9±0.2枚,平均冷冻保存胚胎数为4.3±3.3枚,临床妊娠率A组为50.00%,显示高于B组(30.43%)(P<0.05),继续妊娠率A组为41.67%,显示高于B组(26.09%)(P<0.05);所有患者均未发生无中/重度卵巢过度刺激综合征。A组与B组相比较,获卵率、受精率、优质胚胎率及早期流产率均无统计学差异(P>0.05)。结论:1 000 IU的低剂量hCG能够在COS过程中诱发卵泡成熟,不仅适应于卵巢反应高者,而且也适应于卵巢反应正常者。     

Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans

The aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment.     

Subtle progesterone rise in the single-dose gonadotropin-releasing hormone antagonist (cetrorelix) stimulation protocol in patients undergoing in vitro fertilization or intracytoplasmic sperm injection cycles

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P < 1.2 ng/ml or P ≥ 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P ≥ 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p < 0.001) on the day of hCG injection than the group with P < 1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.     

Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin

OBJECTIVE: To investigate the effect of triggering oocyte maturation with GnRH agonist on corpus luteum function by measuring luteal phase levels of inhibin A and pro-alphaC. DESIGN: Prospective randomized trial. SETTING: In vitro fertilization (IVF) program at a university hospital. PATIENT(S): Infertile women undergoing IVF-ET treatment. INTERVENTION(S): Controlled ovarian hyperstimulation with FSH and GnRH antagonist, triggering of final oocyte maturation with either hCG (n = 8) or GnRH agonist (n = 8), IVF-ET, and collection of blood samples every 2-3 days during the luteal phase. MEASUREMENTS AND MAIN RESULTS: Luteal phase serum levels of inhibin A and pro-alphaC, P, and E(2). RESULT(S): Levels of inhibin A, pro-alphaC, estrogen, and P were significantly lower from day 4 to day 14 after triggering final oocyte maturation by GnRH agonist compared with hCG. Maximal luteal serum inhibin A and pro-alphaC levels were 91.5 +/- 23.6 and 184.1 +/- 23.5 pg/mL in the GnRH agonist-treated women compared with 464.7 +/- 209.1 and 7,351.6 +/- 934.3 pg/mL in women treated with hCG. CONCLUSION(S): Triggering final oocyte maturation with GnRH agonist instead of hCG in IVF cycles dramatically decreases luteal levels of inhibins, reflecting significant inhibition of the corpus luteum function. This effect may explain, at least in part, the mechanism of ovarian hyperstimulation syndrome prevention by the use of GnRH agonist.     

A simplified universal approach to COH protocol for IVF: ultrashort flare GnRH-agonist/GnRH-antagonist protocol with tailored mode and timing of final follicular maturation

Recently, several new promising modifications have been introduced to clinical practice that may simplify and optimize IVF outcome. In the present opinion paper we present a simplified approach to controlled ovarian hyperstimulation protocol (COH), which combines the benefits of the ultrashort flare GnRH agonist/GnRH antagonist protocol and the personalized tailored mode and timing of ovulation triggering, aiming to improve IVF outcome while eliminating of severe OHSS.In patients at risk to develop severe ovarian hyperstimulation syndrome (OHSS), GnRH agonist (GnRHa) trigger if offered for final follicular maturation. While in those achieving ≥20 oocytes, the freeze all policy with the subsequent frozen-thawed embryo transfers (ET) is recommended, in those where less than 20 oocytes are retrieved, patients are re-evaluated 3 days after oocyte retrieval (day of ET) for signs of early moderate OHSS. If no early signs of OHSS developed, one embryo was transferred, and the patients are instructed to inject 1500 IU of HCG. In cases where signs of early moderate OHSS appear, the freeze all policy is recommended.In Patients not at risk to develop severe OHSS- three different modes of concomitant administration of both GnRHa and a standard bolus of hCG (5000–10,000 units) prior to oocyte retrieval were suggested. Standard hCG dose concomitant with GnRHa (dual trigger), 35–37 h before oocyte retrieval is offered to normal responders patients, resulting in improved oocyte/embryo quality and IVF outcome. GnRHa 40 h and standard hCG added 34 h prior to oocyte retrieval (double trigger), respectively are offered to patients demonstrating abnormal final follicular maturation despite normal response to COH. The double trigger results in significantly higher number of oocytes retrieved, higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, higher number of MII oocytes and proportion of MII oocytes per number of oocytes retrieved, with the consequent significantly increased number of top-quality embryos, as compared to the hCG-only trigger cycles. Standard hCG dose concomitant with GnRHa (dual trigger), 34 h before oocyte retrieval should be offered to poor responders patients, aiming to overcome premature luteinization, while achieving high yield of mature oocytes.Further studies are required to support this new concept prior to its implementation as a universal COH protocol to IVF practice.     

Does physicians' experience influence in vitro fertilization success in patients undergoing controlled ovarian hyperstimulation with GnRH antagonists?

In an attempt to examine whether physicians' experience may influence IVF outcome in patients undergoing GnRH antagonist (GnRH-a) controlled ovarian hyperstimulation (COH) protocols, we studied 273 consecutive patients, with a favorable prognosis a priori, admitted to our IVF unit, of whom 88 conceived. The highest pregnancy rate (PR) (46.5%) was observed in patients achieving, on day of hCG administration, an E(2)-to-follicle ratio <100 pg/mL. The timing of hCG administration is crucial in patients undergoing the GnRH-a COH for IVF to optimize success rate.     

Dose of GnRH agonist (nafarelin acetate) affects intrafollicular PAPP-A expression in controlled ovarian hyperstimulation cycle

OBJECTIVE: To determine the effect of dose of GnRH agonist on the follicular environment in controlled ovarian hyperstimulation (COH) cycles. STUDY DESIGN: Twenty-eight IVF patients with normal ovarian function were divided into three groups: group I received GnRHa (nafarelin acetate/Synarel) intranasally at 200 microg daily, group II received 400 microg daily until hCG injection, and group III was given 400 microg daily before the initiation of ovarian stimulation, then 200 microg daily before the day of hCG injection. Serum estradiol, progesterone, and leptin levels were measured on the day of hCG injection. After aspiration, expression of pregnancy-associated alpha-plasma protein (PAPP)-A in the follicular fluid of dominant follicles (>20 mm) was determined by Western blot analysis. RESULTS: No significant difference was noted in serum estradiol, progesterone, and leptin levels. But intrafollicular PAPP-A expression was significantly higher in group II compared to other groups (P<0.05). CONCLUSION: The dose of GnRHa may have an impact on the intrafollicular environment of dominant follicles in COH cycles.     

Does double trigger (GnRH-agonist + hCG) improve outcome in poor responders undergoing IVF-ET cycle? A pilot study

Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on in vitro fertilization (IVF) cycle outcome of poor responder patients. In the present randomized controlled study, poor responder patients, according to the Bologna criteria, undergoing controlled ovarian hyperstimulation (COH) using the gonadotropin-releasing hormone (GnRH) antagonist protocol were randomly assigned to three different final follicular maturation trigger modes and timings: hCG 36?h before oocyte pick-up (OPU) (hCG trigger); GnRH agonist (GnRHag) 36?h before (OPU) and hCG on day of OPU (GnRHag trigger); and GnRHag and hCG, 40 and 34?h prior to OPU, respectively (double trigger). Pregnancy rate, number of oocytes, and top quality embryos (TQEs). Thirty-three poor responder patients were recruited and randomized to the different study groups. While there were no in-between groups’ differences in patients’ demographics and stimulation variables, patients in the double trigger group had a significantly higher number of TQE (1.1?±?0.9 vs. 0.3?±?0.8 and 0.5?+?0.7; p<.02) as compared to the hCG trigger and the GnRH-ag trigger groups, respectively, with an acceptable pregnancy rate. Double trigger offers an additional benefit to poor responder patients. Larger studies are required to support this new concept prior to its implementation to IVF practice.     

Effect of gonadotropin-releasing hormone agonist and antagonist on steroidogenesis of low responders undergoing in vitro fertilization.

The aim of the study was to investigate the cause of the lower estradiol (E(2)) concentration in women treated with gonadotropin-releasing hormone (GnRH) antagonist compared with those treated with agonist protocol in in vitro fertilization (IVF). Thirty patients who were known low responders were prospectively randomized into two equal groups for IVF treatment. Group 1 used GnRH agonist (flare-up) protocol and group 2 used antagonist protocol. The results showed that serum luteinizing hormone (LH) levels were significantly higher in the agonist group during the folliculogenesis stage. Despite this higher LH, serum E(2) levels were significantly higher in the agonist group on cycle day 2 only, not on day 5 or day 9. The significantly higher E(2) level in the agonist group reappeared on the day of administration of human chorionic gonadotropin (hCG). The rate of folliculogenesis in the antagonist group was faster than in the agonist group; therefore their E(2) production should have been higher on hCG day. Furthermore, the rate of decline in E(2) after hCG administration was significantly higher in the antagonist group. These findings, along with the fact that both groups received exogenous LH (human menopausal gonadotropin) that should optimize steroidogenesis and make the difference in E(2) insignificant, enable us to conclude that GnRH antagonists have a suppressive effect on the production of E(2).     

CA-125 Concentrations in the Serum and Pregnancy Outcome in IVF Cycles

Purpose: CA-125 has been proposed as a potential marker for endometrial receptivity in assisted reproduction. This study was designed to evaluate whether the levels of CA-125 in the serum of patients undergoing IVF–embryo transfer (ET) is correlated with the outcome. Methods: Levels of serum CA-125 were measured on the day before and on the day of human chorionic gonadotropin (hCG) administration, ovum pickup (OPU), and ET in 74 patients undergoing 100 IVF cycles between January 1994 and March 1995. Patients were treated with a midluteal-phase gonadotropin-releasing hormone (GnRH) agonist protocol and follicular-phase human menopausal gonadotropin. Results: One hundred oocyte retrievals resulted in 91 ETs, and 22 clinical pregnancies (22%/OPU and 24.2%/ET). The live-born rate was 21%/OPU and 23.1%/ET. Neither the CA-125 serum levels nor their increase from the day of hCG until the day of ET showed any prognostic significance to the outcome of IVF, and they were not correlated with the endometrium thickness or the number of oocytes retrieved or fertilized. Conclusions: The CA-125 serum levels in conventional IVF cycles were not correlated with the IVF outcome and yielded no prognostic information in a GnRH agonist down-regulation protocol.     

Additive hormonelle Therapie bei der assistierten Reproduktion

The article summarizes the knowledge in March 2014 regarding estradiol, progesterone and gonadotropin-releasing hormone (GnRH) agonist administration during the luteal phase after assisted reproductive technologies (ART). The administration of estradiol does not influence the therapeutic outcome. Progesterone supplementation leads to a significantly increased live birth rate after gonadotropin stimulation. Prolonged treatment with progesterone beyond the positive human chorionic gonadotropin (hCG) test has no further beneficial effects on live birth and miscarriage rates. The single administration of a low dose GnRH agonist 5 or 6 days after follicular puncture does not increase the ongoing pregnancy rate in stimulated in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) agonist and antagonist cycles.     

Coordination of antral follicle growth: basis for innovative concepts of controlled ovarian hyperstimulation

Among the key objectives of controlled ovarian hyperstimulation (COH) is the achievement of adequate coordination of multiple follicular growth to trigger ovulation when most of follicles have reached concomitant maturation. However, during the early follicular phase, early antral follicles present noticeable size heterogeneities that may be amplified during COH. To challenge the hypothesis that this phenomenon results, at least in part, from the early exposure of antral follicles to gradient follicle-stimulating hormone (FSH) levels during the preceding late luteal phase, we conducted three clinical studies. First, we artificially lowered luteal FSH levels by administering estradiol (E (2)) and measured follicular characteristics on the subsequent day 3. Second, we verified whether luteal E (2) administration could promote the coordination of follicular growth during COH and improve its results. Third, we assessed the effects of premenstrual gonadotropin-releasing hormone (GnRH) antagonist administration on follicular characteristics during the early follicular phase. Our results showed that luteal FSH suppression by either E (2) or GnRH antagonist administration reduces the size and improves the homogeneity of early antral follicles during the early follicular phase, an effect that persists during COH. Coordination of follicular development may optimize ovarian response to short GnRH agonist and antagonist protocols, and constitutes an attractive approach to improving their outcome.