Liver Cancer and Pregnancy: A Review of the Literature.

BACKGROUND/AIM: Liver cancer constitutes one of the leading cancers globally. During pregnancy, however, liver cancer is an absolute rarity, with very few cases reported in the international literature. The aim of the present review was to provide a useful update and summarize all case studies of liver cancer in pregnancy published between 2012-2023. MATERIALS AND METHODS: A literature review was conducted using the MEDLINE, LIVIVO, and Google Scholar databases. Solely case reports and case studies written in the English language that explicitly reported on the presence of histologically confirmed HCC or intrahepatic cholangiocarcinoma during pregnancy were included in the data analysis. RESULTS: After detailed evaluation, a total of 35 reported cases of liver cancer during pregnancy were identified, hence bringing the total number of reported cases globally to 83. Oncological challenges during pregnancy call for an interdisciplinary approach. Although the desire to preserve the pregnancy should be taken into consideration, specialists need to evaluate maternal and fetal well-being and choose the optimal oncological treatment with the least dangers for both the maternal and fetal safety. CONCLUSION: The present review proves that, despite its scarcity, liver cancer may always occur during pregnancy and clinicians should, therefore, remain vigilant and endeavor to detect and evaluate any hepatic mass or symptoms of liver cancer promptly and exhaustively.

Is There an Association Between Circulating Kisspeptin Levels and Ovarian Reserve in Women of Reproductive Age?

BACKGROUND/AIM: To investigate the possible association of kisspeptin levels with the ovarian reserves of women of reproductive age. PATIENTS AND METHODS: Eighty women aged 19-40 participated after signing an informed consent. Of these, 74 were finally included as in 6 women the blood samples were considered inappropriate due to hemolysis. They were divided into three main groups according to their ovarian reserve patterns: women with adequate ovarian reserves (Group A - AOR) (n=30), women with increased ovarian reserves (Group B - PCOS) (n=31), and women with diminished ovarian reserves (Group C - DOR) (n=13). RESULTS: Women with diminished ovarian reserves had statistically significantly increased age and FSH compared to the other two groups. No statistically significant difference was found between the three groups for estradiol and thyroid stimulating hormone. Moreover, body mass index, luteinizing hormone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone, anti-Mullerian hormone (AMH), and antral follicle count (AFC) were increased in group B compared to the other two groups. AMH and AFC were decreased in women with diminished ovarian reserves compared to the other two groups, as expected. The comparison of kisspeptin levels between the three groups showed that kisspeptin levels were increased in women with diminished ovarian reserves, compared to the other two groups, but without a statistically significant difference. However, kisspeptin levels in group C were statistically significantly higher than those in group A. CONCLUSION: There are no strong indications that kisspeptin levels are associated with the ovarian reserve in women of reproductive age.

Role of leptin, adiponectin, and kisspeptin in polycystic ovarian syndrome pathogenesis.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) affects 5-20% of females and is the most common cause of anovulatory infertility. Leptin seems to have an important role in reproduction. Many reproductive pathologies such as preeclampsia, PCOS, and endometriosis are associated to plasma adiponectin levels. Kisspeptin levels are increased in PCOS women. EVIDENCE ACQUISITION: A review of the literature was completed through the PubMed database aiming to find articles regarding leptin, adiponectin and kisspeptin and if they are related to PCOS pathogenesis. EVIDENCE SYNTHESIS: Even today it is not clear what is the role of leptin in women with PCOS, although most of the researchers found increased levels of leptin as well as leptin resistance in PCOS (both obese and lean individuals). Many more longitudinal studies should be done to discover the usefulness of measuring adiponectin in prepubertal women who apparently have a possibility to develop PCOS to find out if they finally develop PCOS. Most of the researchers found that PCOS women have decreased levels of adiponectin unrelated to BMI levels. Nevertheless, not all studies had the same result. Moreover, it is necessary more studies to be made to investigate the connection between kisspeptin and other metabolic factors such as LH and insulin resistance. CONCLUSIONS: In general, it remains inconclusive whether leptin, adiponectin, and kisspeptin can be used as clinical and/or biochemical markers of PCOS. Therefore, it is essential to review the current data with regards to the association between PCOS and circulating leptin, adiponectin, and kisspeptin in women with PCOS.

Imbalance of growth factors mRNA expression associated with oxidative stress in the early pregnancy loss.

OBJECTIVE: The aim of this study was to examine the role of growth factors associated with angiogenesis and oxidative stress in the pathogenesis of spontaneous miscarriage. METHODS: We performed a comparative mRNA expression analysis of VEGF, PlGF, Flt-1, Angiogenin and Endoglin using Real-Time PCR, in the placenta and decidua collected from 12 patients presenting with spontaneous abortion and from 14 women undergoing induced abortion, during the first and second trimester of pregnancy. RESULTS: The mRNA expression of Flt-1 was significantly upregulated in the placenta of spontaneous abortions (5.17-fold, IQR: 2.72-9.11, p < 0.01). The placental expression of the soluble isoforms of Flt-1, sFlt-1 e15a and sFlt-1 i13, was also significantly upregulated in spontaneous abortions (sFlt-1 e15a: 2.35-fold, IQR: 0.98-2.83, p < 0.01; sFlt-1 i13: 3.47-fold, IQR: 2.37-5.08, p < 0,05). Placental tmFlt-1, PlGF and Endoglin showed a tendency of higher expression levels in spontaneous abortions, although they did not reach statistical significance (tmFlt-1: 7.42-fold, IQR: 3.58-14.32; PlGF: 2.36-fold, IQR: 0.90-4.12; Endoglin: 1.97-fold, IQR: 1.18-2.43). VEGF and Angiogenin mRNA expression in induced, as well as in spontaneous abortions, did not convey any statistically significant difference. In the decidua, the expression levels of Flt-1 and its splice variants sFlt-1 e15a, sFlt-1 i13 and tmFlt-1 did not show any statistically significant differences, as was the case for the rest of the herein examined growth factors. CONCLUSIONS: In this study, we observed higher levels of sFlt-1 mRNA expression in the placenta of spontaneous abortions, while expression of other growth factors in placenta and decidua remained constant. This suggests that an imbalance of sFlt-1 expression in the placenta might contribute to the pathogenesis of spontaneous abortion, probably via oxidative stress, providing a possible biomarker for prompt identification of this condition.

BRCA 1, 2 mutation and earlier menopause: could BRCA 1,2 be used as predictor of menopause?

INTRODUCTION: Many studies have shown that BRCA mutation is not only related to cancer but also to ovarian aging. Studies in both human and mice oocytes have shown that Double-strand breaks (DSBs) accumulate with age. EVIDENCE ACQUISITION: A review of the literature was completed through the PubMed database aiming to find articles regarding BRCA 1,2 mutation and if they are related to early menopause in order to use them as predictive biomarkers in the near future. The research used keywords in numerous combinations, such as "BRCA 1,2 mutation," "menopause," "ovarian reserves," "AMH," "genome-wide association studies," and "biomarkers." The literature was limited in this specific topic. The initial research found 16 screened articles, 7 of which were not included because there were not relevant, as far as publications in non-English language. EVIDENCE SYNTHESIS: Genome-wide association studies (GWAS) have found 44 genetic loci that are related to variations when a female is about to have menopause. BRCA1 is involved in these 44 loci that are associated with the age of menopause. This review has gathered all results of literature search about the association between BRCA genes and early menopause. Most of the articles found that women with BRCA mutation have earlier menopause compared to non-carriers. CONCLUSIONS: In conclusion, in the near future BRCA1,2 genes could be used as predictive biomarkers of menopause.

Investigational Drug Treatments for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) and accounts for 10-20% of cases. Due to the lack of expression of several receptors, hormone therapy is largely ineffective for treatment purposes. Nevertheless, TNBC often responds very well to chemotherapy, which constitutes the most often recommended treatment. New beneficial targeted therapies are important to be investigated in order to achieve enhanced outcomes in patients with TNBC. This review will focus on recent therapeutic innovations for TNBC, focusing on various inhibitors such as phosphoinositide 3-kinase (PI3K) pathway inhibitors, poly-ADP-ribosyl polymerase (PARP) inhibitors, aurora kinase inhibitors, histone deacetylase inhibitors (HDACIs), and immune checkpoint inhibitors.

Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an extremely diverse group of breast tumors, with aggressive clinical behavior, higher rates of distant recurrence and worse overall survival compared to other types of breast cancers. The genetic, transcriptional histological and clinical heterogeneity of this disease has been an obstacle in the progression of targeted therapeutic approaches, as a ubiquitous TNBC marker has not yet been discerned. In terms of that, current studies focus on the classification of TNBC tumors in subgroups with similar characteristics in order to develop a treatment specialized for each group of patients. To date, a series of gene expression profiles analysis in order to identify the different molecular subtypes have been used. Complementary DNA microarrays, PAM50 assays, DNA and RNA sequencing as well as immunohistochemical analysis are some of the methods utilized to classify TNBC tumors. In 2012, the Cancer Genome Atlas (TCGA) Research Network conducted a major analysis of breast cancers using six different platforms, the genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays, in order to assort the tumors in homogenous subgroups. Since then, an increasing number of breast cancer data sets are being examined in an attempt to distinguish the classification with biological interpretation and clinical implementation. In this review, the progress in molecular subtyping of TNBC is discussed, providing a brief insight in novel TNBC biomarkers and therapeutic strategies.

Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies.

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) and unfortunately is not associated with good prognosis. Treatment of breast cancer mainly depends on chemotherapy, due to the lack of specifically approved targeted therapies for TNBC. It is of paramount importance to find new therapeutic approaches, as resistance to chemotherapy frequently occurs. Herein, we present clinical studies published within the last five years, in order to reveal possible targeted therapies against TNBC. We aimed to discuss factors against TNBC, such as tyrosine kinase inhibitors, anti-androgens, poly ADP-ribose polymerase-1 (PARP-1) inhibitors, anti-angiogenic factors, immune checkpoints and histone deacetylase inhibitors (HDACI). Furthermore, the PI3K/AKT/mTOR pathway seems to be a promising field for the development of new anti-TNBC targeted therapies. Data from 18 clinical trials with patients suffering from TNBC were summarized and presented descriptively.

Genotoxic effect of tocolytic drug ritodrine in combination with smoking during pregnancy.

OBJECTIVE: Tocolytic drugs are used widely in order to prevent preterm birth. Ritodrine, is the only food and drug administration (FDA) approved drug for tocolytic use. We estimated the cytogenetic effect of ritodrine administered as maternal therapy, alone or in combination with smoking, in women and their neonates. METHODS: Lymphocyte and fibroblasts cultures were evaluated and three indices were analyzed; sister chromatid exchanges (SCEs), proliferation rate index (PRI) and mitotic index (MI) as well as average generation time (AGT) and population doubling time (PDT). Campothacin (CPT-11) was used as a positive control. RESULTS: Administration of ritodrine up to a month revealed significant reduction of SCEs/cell in neonates in the presence or absence of the mutagenic agent. A statistical significant increase on SCEs, for mothers and neonates, was noticed in neonate's lymphocytes when tocolytic therapy was over a month. Ritodrine revealed a cytoprotective action against smoking when the two factors were combined, but the synergistic action of ritodrine with smoking increased genotoxicity, cytostaticity and cytotoxicity of neonates after long administration (1-3 months). CONCLUSIONS: The time-depended genotoxic, cytostatic and cytotoxic action of ritodrine alone or in combination with smoking suggests that its administration should not exceed the time period of a month.

Effect of maternal smoking during pregnancy on fetus: a cytogenetic perspective.

OBJECTIVE: The examination of the genotoxic, cytostatic and cytotoxic effects of smoking during pregnancy. METHOD: Lymphocyte cultures of peripheral blood were received from 20 women who smoked during pregnancy as well as umbilical cord blood of their newborns. Fluorescence Plus Giemsa staining technique was used in order to perform cytogenetic analyses for three indices, Sister Chromatid Exchanges (SCEs), Proliferation Rate Index (PRI) and Mitotic Index (MI). To reveal any underlying chromosome instability, CPT-11 was used as a positive control. RESULTS: Newborns whose mothers smoke during pregnancy had increased SCEs levels on their lymphocytes when they were exposed to the mutagenic agent CPT-11 (p < 0.01) compared with newborns lymphocytes exposed to the same agent with non-smoking mothers. Also, mothers smoking during pregnancy had increased SCE levels when their lymphocytes were exposed to CPT-11 (p < 0.01) compared with non smoking mothers whose lymphocytes were exposed to the same agent. In both groups newborns appeared as having decreased (p < 0.01) spontaneous SCEs levels compared with the corresponding SCE rates of their mothers. Decreases of PRIs and MIs are observed in mothers compared to their newborns. CONCLUSION: Smoking during pregnancy can promote cytogenetic damage in newborn's DNA, causing chromosome instability. The clinical importance of this indirect damage lies in the fact that this type of damage can act synergistically with other environmental and/or chemical mutagenic substances possibly leading to carcinogenicity.

Soluble FAS and FAS ligand levels in seminal plasma: association with basic parameters of semen analysis.

BACKGROUND/AIM: Binding of FAS ligand (FASL) to its physiological receptor FAS, induces the activation of caspase-8, which triggers cell death. The FAS-FASL system regulates germ cell death. In this study, the role of the FAS-FASL system in male infertility was examined. PATIENTS AND METHODS: 72 samples were used (age=38.76 ± 9.06 years). Basic semen analysis was performed according to the WHO Laboratory Manual. Soluble (s) forms of FAS and FASL were measured in seminal plasma using commercially available immunoassay kits. RESULTS: Among the examined samples, 24 were normal and 48 abnormal, as evaluated by basic semen analysis. sFAS and sFASL levels in abnormal samples were slightly higher than in the normal ones. In all samples, sFAS correlated negatively with pH. In normal samples, sFAS was positively correlated with sperm concentration. In abnormal samples, sFAS strongly correlated with sFASL. CONCLUSION: Both factors of the FAS system were detected in seminal plasma. Further studies are necessary to shed light into the possible role of FAS-FASL system in male infertility.

The effects of cetrorelix and triptorelin on the viability and steroidogenesis of cultured human granulosa luteinized cells.

BACKGROUND: We investigated the effects of the gonadotropin-releasing hormone (GnRH) agonist triptorelin as well the GnRH antagonist cetrorelix those of on the viability and steroidogenesis in human granulosa luteinized (hGL) cell cultures. MATERIALS AND METHODS: The hGL cells were obtained from 34 women undergoing ovarian stimulation for IVF treatment. The cells were cultured for 48 h with or without 1 nM or 3 nM of cetrorelix or triptorelin in serum-free media. The cell viability was evaluated by the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The concentrations of estradiol and progesterone in culture supernatants were measured by ELISA. RESULTS: Treatment with triptorelin slightly increased cell viability, whereas treatment with 3 nM cetrorelix led to a significant decrease. Estradiol concentrations were reduced with 3 nM triptorelin. Cultures treated with high-dose of either cetrorelix or triptorelin tended to secrete less progesterone than controls. CONCLUSION: Cetrorelix significantly reduces the viability of hGL cells. Triptorelin and cetrorelix may have minor effects on steroidogenesis. These results suggest that GnRH analogues may influence ovarian functions.

Concentrations of inflammatory cytokines and the outcome in ICSI cycles.

UNLABELLED: The aim of this study was to measure circulating and intrafollicular concentrations of three inflammatory cytokines from women undergoing ovarian stimulation in order to determine their prognostic value in the outcome of intracytoplasmic sperm injection/embryo transfer cycles. MATERIALS AND METHODS: A total of 72 women following ovarian stimulation and intracytoplasmic sperm injection were included. Blood serum samples were drawn at the day of chorionic gonadotropin administration. Follicular fluids were collected at the day of oocyte retrieval. The total fractions of tumor necrosis factor alpha, interleukin (IL)-1beta and IL-6 were measured with commercially available immunoassays. RESULTS: The concentrations of IL-1beta, both in serum and follicular fluids, were significantly different between ICSI cycles that resulted in pregnancy and those that failed. The concentrations of the other two cytokines did not significantly differ between successful and unsuccessful cycles. CONCLUSION: The circulating and intrafollicular concentrations of IL-1beta seem to be related to the pregnancy outcome in ICSI cycles of healthy women.

Serum pattern of circulating adipokines throughout the physiological menstrual cycle.

This study investigated the serum levels of resistin, adiponectin and leptin during the physiological menstrual cycle. Sixteen women (age: 19-30 years; body mass index: 19.46-24.9) with regular menstrual cycles participated. Fasting blood samples were collected on alternate days throughout a full menstrual cycle. Mean resistin concentrations were slightly higher during the luteal phase (5.30+/-0.23 ng/ml) compared to the follicular (4.68+/-0.07 ng/ml) and midcycle (4.86+/-0.09 ng/ml) phases (p=0.032). Mean leptin concentrations during the follicular phase (18.14+/-0.28 ng/ml) were significantly lower compared to the midcycle (21.79+/-0.29 ng/ml, p=0.006) and luteal phases (23.75+/-0.64 ng/ml, p<0.001). The variation of adiponectin concentrations throughout the menstrual cycle was not significant. According to the results, circulating resistin, likewise leptin concentrations vary significantly during the physiological menstrual cycle presenting with higher values during the luteal phase. This pattern, although its physiological importance is not clear, suggests that resistin, likewise to leptin, may have a role in the regulation of cyclic female reproductive functions. The stable adiponectin concentrations throughout the menstrual cycle indicate that this adipokine probably does not play a considerable role in female reproductive functions.

Erythropoietin and growth factors exhibit differential angiogenic potential in mouse heart.

BACKGROUND: The possible angiogenic effect of recombinant human erythropoietin (rHuEpo) and several possibly angiogenic cytokines such as basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGIF) and vascular endothelial growth factor (VEGF) was investigated in mouse heart. MATERIALS AND METHODS: Mice were divided into five groups (n = 7/group): A, control; B, rHuEpo-treated; C, (aFGF-treated); D, (VEGF-treated); E, (bFGF-treated). The antibody mouse anti-human CD31 was used to evaluate the vessels present in histological preparations. RESULTS: The results show a significant increase of the vessel number per optical field in the rHuEpo-treated, the bFGF-treated and the VEGF-treated animals compared to controls whereas aFGF did not show any significant angiogenic activity. CONCLUSION: Erythropoietin has a significant angiogenic effect in the mouse heart, similar to the effect of other angiogenic factors such as bFGF and VEGF whereas aFGF does not exhibit any effect.

Ghrelin in pathological conditions.

The recently identified gastric hormone ghrelin was initially described as a natural Growth Hormone Secretagogue Receptor ligand. Apart from ghrelin's first discovered action, which was the stimulation of Growth Hormone release, implications for many other functions have been reported. It seems that ghrelin exhibits an important role in conditions related to processes regulating nutrition, body composition and growth, as well as heart, liver, thyroid or kidney dysfunction. In this review, current available knowledge about ghrelin's role in various pathological conditions is presented.

The levels of steroid hormones and cytokines in individual follicles are not associated with the fertilization outcome after intracytoplasmic sperm injection.

OBJECTIVE: To investigate the association between the levels of two steroid hormones and eight cytokines in fluids from individual follicles and the fertilization outcome of the oocytes derived from the same follicles. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Forty-three women participating in intracytoplasmic sperm injection (ICSI)/ET cycles. INTERVENTION(S): The ovarian stimulation followed the multidose GnRH antagonist protocol. ICSI was performed in mature oocytes. The concentrations of estradiol, progesterone, tumor necrosis factor-alpha, interleukin (IL) -1beta, IL-6, vascular endothelial growth factor, leptin, basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I were measured by immunoassay methods in the follicles from which the mature oocytes were derived. MAIN OUTCOME MEASURE(S): The concentrations of the above hormones and cytokines in individual follicles and the fertilization outcome of the oocytes derived from the same follicles. RESULT(S): The intrafollicular concentrations of the above factors were not significantly associated with the fertilization outcome. These factors were not correlated with embryo quality, with the exception of leptin, which was weakly associated with embryo score (R = 0.276). CONCLUSION(S): The intrafollicular concentrations of the above factors cannot predict the fertilization outcome after ICSI.

Gonadotropin-releasing hormone in the ovary.

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are expressed, apart from the hypothalamus, in various compartments of the human ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the proliferation, and induce apoptosis of ovarian cells. In this review, the biology of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct effects of GnRH analogues in ovarian cells are discussed.

Erythropoietin enhances angiogenesis in an experimental cyclosporine A-induced nephrotoxicity model in the rat.

1. Erythropoietin (EPO) is a hormone regulating the proliferation and differentiation of erythroid precursor cells. The hypothesis that haematopoietic and endothelial cells share a common haemanglioblast progenitor among others is based on the finding that both cell lineages express cell surface antigens, such as CD31 and CD34. 2. In the present study, we investigated the angiogenic potential of recombinant human erythropoietin on cyclosporine A (CsA)-induced nephrotoxicity in the rat kidney and compared it with the effect of basic fibroblast growth factor (bFGF), a well-known angiogenic factor. 3. Rats were divided into five groups: A (control), B (EPO treated), C (CsA treated), D (CsA + EPO treated) and E (CsA + bFGF treated). Mouse anti-human CD31 and CD34 antibodies were used to evaluate the kidney vessels present in histological preparations. 4. Glomerular and peritubular capillaries in Group B (EPO) were increased compared with the control (Group A; P < 0.05). Reduction of the same kidney vessels (glomerular and peritubular capillaries) in Group C (CsA; P < 0.05) compared with controls was observed, whereas in Groups D (CsA + EPO treated) and E (CsA + bFGF treated), capillaries were increased compared with Group C (CsA; P < 0.05). 5. Erythropoietin has a significant angiogenic effect in rat kidney with CsA-induced nephrotoxicity, similar to the effect of the other angiogenic factor bFGF.

Cytokine and hormonal profile in blood serum and follicular fluids during ovarian stimulation with the multidose antagonist or the long agonist protocol.

BACKGROUND: The aim of our study was to explore cytokine and hormonal profiles in blood and follicular fluids from normal women stimulated with either the multidose antagonist or the long agonist protocol. METHODS: Fifty-six patients were stimulated with the multidose antagonist protocol and 12 with the long agonist protocol. Interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha), leptin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), estradiol (E(2)), progesterone and testosterone levels were measured in serum and follicular fluids by immunoassays. RESULTS: The two treatment groups had similar cytokine concentrations in serum. The intrafollicular concentrations of IL-1beta, IL-6, VEGF and leptin were also similar in the two groups. The concentrations of bFGF in follicular fluids from the antagonist group (169.5 +/- 113.2 ng/ml) were lower than those from the agonist group (249.7 +/- 119.8 ng/ml). bFGF concentrations were correlated with the amount of administered gonadotrophins (R = 0.364, P < 0.01) which was significantly lower in the antagonist group (antagonist group: 2037.7 +/- 725.8 IU; agonist group: 2836.4 +/- 1163.5 IU). CONCLUSIONS: Normal women stimulated with either the multidose antagonist or the long agonist protocol generally have similar cytokine profiles in serum and follicular fluids. The intrafollicular levels of bFGF tend to be lower in antagonist cycles because of the lower amount of administered gonadotrophins.