The effect of male and female factor infertility on women's anxiety, depression, self-esteem, quality of life and sexual function parameters: a prospective, cross-sectional study from Turkey.

OBJECTIVES: Despite the development of diagnosis and treatment methods, the psychological effects of infertility on women were not adequately addressed. This study investigated the effect of male and female factor infertility on women's anxiety, depression, self-esteem, quality of life, and sexual function parameters. METHODS: In this prospective, cross-sectional study, 480 women [n = 234, with male factor infertility (MFI) (MFI group) and n = 246, with female factor infertility (FFI) (FFI group)], who could not conceive despite unprotected intercourse for 1 year, and 242 fertile healthy women (control group) who had children within the last 1 year were included. Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Rosenberg Self Esteem Scale (RSES), Fertility Quality of Life (FertiQol) and Female Sexual Function Index (FSFI) questionnaires were used for patients' evaluation. RESULTS: RSES, BAI and BDI-II scores were significantly higher and FSFI score was significantly lower in the FFI group compared to other groups. RSES, BAI and BDI-II scores were also significantly higher and FSFI score was significantly lower in the MFI group compared to the control group. FertiQol total score was significantly lower in the FFI group compared to the MFI group. RSES score was positively correlated with BDI-II and BAI scores; however, it was negatively correlated with FertiQol and FSFI scores. CONCLUSIONS: The negative psychological effects of infertility are ignored by many centres, especially in the treatment process of infertility. Regardless of the infertility factor (male or female), we believe that psychological support should be given to all women to improve their life quality.

Antithyroid antibodies may predict serum beta HCG levels and biochemical pregnancy losses in euthyroid women with IVF single embryo transfer.

OBJECTIVE: To investigate the relationship between thyroid autoimmunity and early pregnancy serum ß-HCG levels in intracytoplasmic sperm injection patients. METHODS: The study subjects were 85 female euthyroid patients undergoing intracytoplasmic sperm injection embryo transfer cycles with GnRH antagonist treatment. Patients who received transfer of more than one embryo, those with serum TSH levels of greater than 2.5 IU/ml and subjects using levothyroxine were excluded. Normal responder patients under the age of 40 years were randomly selected from the patient files retrospectively. Subjects were divided into two groups: those with autoimmune thyroid disease (thyroid autoimmunity group; n = 39) and those without the disease (control group; n = 46). RESULTS: The age, body mass index, trial number, total rFSH treatment dose, the number of cumulus oophorus complexes, number of metaphase II oocytes, and number of 2-pronuclei embryos were similar in the thyroid autoimmunity and control groups. Serum ß-HCG levels measured on the 14th day after oocyte pickup were significantly lower in the thyroid autoimmunity group than in the control group (93.8 ± 35.8 versus 128.5 ± 55.8 mlU/ml, respectively; p < .001). The miscarriage rate was higher in the thyroid autoimmunity group than in the control group (34.4% versus 21.7%, respectively; p = .034). CONCLUSION: We found that early-stage pregnancy serum ß-HCG hormone levels among euthyroid patients undergoing intracytoplasmic sperm injection were lower in subjects with thyroid autoimmunity than in those without thyroid autoimmunity. This result, reported for the first time in the literature on euthyroid pregnant women with thyroid autoimmunity, may be predictor of early pregnancy losses in pregnant women with thyroid autoimmunity.Key messageIn intracytoplasmic sperm injection (ICSI)/IVF patients, due to lack of evidence-based data about the relationship between thyroid autoimmunity and pregnancy loss the current research was conducted. Early-stage pregnancy serum ß-HCG hormone levels in euthyroid ICSI patients with thyroid autoimmunity are lower than those without autoimmunity which may be associated with early pregnancy losses.

Spectroscopy analysis of endometrial metabolites is a powerful predictor of success of embryo transfer in women with implantation failure: a preliminary study.

OBJECTIVE: To investigate whether prior endometrium spectroscopy predicts the success of embryo transfer in patients with recurrent implantation failure (RIF). MATERIALS AND METHODS: Twenty women with RIF who were scheduled for IVF-ET and six fertile women were included the study. All women with RIF and fertile controls underwent endometrium spectroscopy before embryo transfer. A multi-voxel spectroscopy sequence was used for the detection of choline (Cho), creatine (Cr), lactate, and lipids. Women with RIF were divided into two subgroups as successful (n = 8) and unsuccessful RIF (n = 12) according to both Cho and Cr metabolite characteristics and whether pregnancy was achieved. Associations between the metabolite intensities of the RIF subjects and the implantation rate (IR) and clinical pregnancy rate (CPR) were assessed. RESULTS: While 8 of 20 RIF cases became pregnant, pregnancy could not be achieved in 12 cases. The common spectroscopy finding in all 8 cases who conceived was high Cho and low lactate. The main metabolite change detected in 12 patients who could not conceive was the increase in lactate and lipid signals. The cutoff value of Cho, Cr, lactate and lipid were 1.01 ppm, 1.44 ppm, 0.86 ppm and 1.22 ppm respectively in patients who achieved pregnancy following ET. A positive and significant correlation was found between Cho and Cr intensities and IR or CPR. CONCLUSIONS: Receptive endometrium represents some specific metabolites in spectroscopy that can be used for prediction of the success or failure of embryo transfer in women suffering implantation failure.

The impact of timing for estrogen supplementation in polycystic ovary syndrome patients undergoing primed in vitro maturation.

OBJECTIVE: This study aims to determine the effects of early and late onset estrogen supplementation on the immature oocyte retrieval, fertilization and clinical pregnancy rates in follicle stimulating hormone (FSH) and human chorionic hormone (hCG) primed in vitro maturation (IVM) cycles of the patients with polycystic ovary syndrome (PCOS). METHODS: This is a retrospective analysis of 161 patients with PCOS who underwent FSH and hCG primed IVM. Group 1 included 120 patients who received early onset estrogen supplementation while group 2 consisted of 41 patients who had late onset estrogen supplementation in primed IVM cycles. Immature oocyte (germinal vesicle and/or metaphase I) retrieval and fertilization rates were the primary outcomes, whereas clinical pregnancy and live rates were the secondary outcomes. RESULTS: Group 1 patients had significantly higher body mass index and more previous IVF attempts (p = 0.001 and p = 0.008, respectively). All of the retrieved oocytes from the PCOS patients were either germinal vesicle or metaphase I oocytes and there were no metaphase II oocytes among the retrieved oocytes. Both groups had statistically similar numbers of metaphase I and fertilized oocytes (p > 0.05 for both). However, group 1 patients had significantly lower number of germinal vesicle oocytes but significantly higher number of metaphase II oocytes (p = 0.001 for both). Both groups had statistically similar fertilization (85.0% vs 78.0%), clinical pregnancy (49.2% vs 43.9%) and live birth (37.5% vs 39.0%) rates (p > 0.05 for all). CONCLUSION: Early onset estrogen supplementation appears to improve the quality of retrieved immature oocytes and contribute to the maturation of oocytes in stimulated IVM cycles.

Surgical removal of FIGO type 0 and 1 fibroids ameliorates the expression of endometrial proinflammatory transcription factors and receptivity modulators.

OBJECTIVE: To reveal whether hysteroscopic removal of the International Federation of Gynecology and Obstetrics (FIGO) types 0 and 1 fibroids makes any changes in the expression of homeobox genes (HOXA10, HOXA11), leukemia inhibitory factor, and nuclear factor-kappa B (NF-kB). DESIGN: A case-control study. SETTING: University-based in vitro fertilisation center. PATIENT(S): This study consisted of a total of 29 participants, 21 with FIGO types 0 and 1 fibroids and 8 with normal uterine cavity without fibroids. INTERVENTION(S): Patients in FIGO types 0 and 1 fibroids group underwent hysteroscopic myomectomy. The patients in the control group underwent laparoscopic tubal ligation. Endometrial cells were collected by flushing method from all participants before and 3 months after myomectomy. Real-time polymerase chain reaction was used to detect HOXA10, HOXA11, and LIF mRNA expressions in endometrial flushing samples. The relative expressions of homeobox and LIF mRNA were calculated with comparative ΔCt method. Endometrial NF-kB concentration was measured quantitatively by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURE(S): To compare endometrial HOXA10, HOXA11, and LIF mRNA expressions as well as endometrial NF-kB concentration before and after myomectomy. RESULT(S): Premyomectomy NF-kB levels of type 0 (4.22 ± 1.02 ng/mL) and type 1 fibroid (6.44 ± 2.30 ng/mL) were significantly higher than the values of control group (0.54 ± 0.10 ng/mL). Surgical removal of type 0 and 1 fibroids resulted in a significant decrease in endometrial NF-kB levels (1.33 ± 0.02 ng/mL vs 1.65 ± 0.27 ng/mL, respectively). In type 0 fibroid group, after myomectomy, there was a 11.1-fold increase in HOXA10 mRNA, 4.23-fold in HOXA11 mRNA, and 7.63-fold in LIF mRNA. In the type 1 fibroid group, after myomectomy, there was a 16.3-fold increase in HOXA10 mRNA, 8.34-fold in HOXA11 mRNA, and 9.38-fold in LIF mRNA. A nonsignificant change was detected in homeobox and LIF mRNA after tubal sterilization. A negative and significant correlation was found between endometrial NF-kB and HOXA10 (r=-0.67), HOXA11 (r=-0.71) and LIF (r=-0.54). CONCLUSION(S): High proinflammatory NF-kB concentration and low homeobox and LIF mRNA expressions were detected in the presence of type 0 or 1 fibroids that returned to normal values after hysteroscopic myomectomy.

Correlation of serum leptin and ghrelin levels with endocrine and reproductive parameters in women with clomiphene citrate resistant polycystic ovary syndrome.

Objective: To investigate the changes in serum ghrelin and leptin levels in patients with clomiphene-resistant polycystic ovary syndrome (PCOS). Materials and Methods: Thirty-five patients who could not achieve ovulation or pregnancy despite using 150 mg/day of clomiphene citrate (CC) participated in the study. Thirty-five patients who were compatible with the study group in terms of age and body mass index (BMI) but did not have clinical and laboratory findings of PCOS constituted the control group. On the third day of the cycle, in addition to the basal hormone profile, ghrelin and leptin levels were also measured. Patients in both groups went to IVF/ICSI. Basal hormone values, leptin, ghrelin, metabolic, demographic parameters, and clinical pregnancy rates were correlated. Results: Patients in both groups were recorded to be similar in terms of age (29.4±0.11 vs 28.5±7.30), BMI (24.3±3.07 vs 23.8±1.55), and infertility time (6.14±4.30 vs 6.03±1.28). Serum ghrelin levels of the PCOS group were significantly lower than the control group (0.48±2.21 vs 1.19±4.02) Serum leptin levels of the PCOS group were significantly higher than the control patients (45.6±304 vs 16.5±0.32). Serum leptin levels and BMI (r=0.65, p<0.01) A positive correlation was found between luteinizing hormone (LH) (r=0.53, p<0.02), and insulin resistance (r=0.74, p<0.03). There was a negative (r=-0.76, p<0.03) correlation between serum ghrelin and LH. A positive and significant correlation was found between serum ghrelin, testosterone, mature oocyte, and implantation rates. Conclusion: Serum ghrelin correlates with fertility outcomes in women with CC-resistant PCOS undergoing IVF/ICSI.

Ovarian drilling down-regulates endometrial nuclear factor-κB p65 expression in women with PCOS: A prospective case-control study.

Objective: To investigate the impact of laparoscopic ovarian drilling (LOD) on the expression of endometrial NFκB p65 (Rel A) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). Materials and Methods: The study group comprised 25 normal-weight women with PCOS undergoing LOD and 14 control women without PCOS. Endometrial NF-κB p65 levels evaluated before and after LOD following immunohistochemical staining. The semiquantitative method was used to evaluate the intensity of NF-κB p65 levels. NF-κB p65 was found to higher in the endometrium of patients with PCOS compared to controls. LOD leads to significant down-regulation in endometrial NF-κB p65 expression. NF-κB p65 expression of PCOS and fertile control were similar after LOD. After LOD, H-score values decreased approximately 3-fold. The H-score of the control subjects was lower than the preoperative and postoperative H-score values of the control women with ovarian cyst. Results: Expression of endometrial NF-κB p65 did not change following ovarian cystectomy. The laterality of the ovarian cyst did not cause any change in preoperative H-score values. Conclusion: By downregulating the endometrial NF-κB p65 expression LOD improved physiological inflammation in women with PCOS.

Oocyte maturation abnormalities - A systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina.

A small proportion of infertile women experience repeated oocyte maturation abnormalities (OMAS). OMAS include degenerated and dysmorphic oocytes, empty follicle syndrome, oocyte maturation arrest (OMA), resistant ovary syndrome and maturation defects due to primary ovarian insufficiency. Genetic factors play an important role in OMAS but still need specifications. This review documents the spectrum of OMAS and to evaluate the multiple subtypes classified as OMAS. In this review, readers will be able to understand the oocyte maturation mechanism, gene expression and their regulation that lead to different subtypes of OMAs, and it will discuss the animal and human studies related to OMAS and lastly the treatment options for OMAs. Literature searches using PubMed, MEDLINE, Embase, National Institute for Health and Care Excellence were performed to identify articles written in English focusing on Oocyte Maturation Abnormalities by looking for the following relevant keywords. A search was made with the specified keywords and included books and documents, clinical trials, animal studies, human studies, meta-analysis, randomized controlled trials, reviews, systematic reviews and options written in english. The search detected 3,953 sources published from 1961 to 2021. After title and abstract screening for study type, duplicates and relevancy, 2,914 studies were excluded. The remaining 1,039 records were assessed for eligibility by full-text reading and 886 records were then excluded. Two hundred and twenty seven full-text articles and 0 book chapters from the database were selected for inclusion. Overall, 227 articles, one unpublished and one abstract paper were included in this final review. In this review study, OMAS were classified and extensively evaluatedand possible treatment options under the light of current information, present literature and ongoing studies. Either genetic studies or in vitro maturation studies that will be handled in the future will lead more informations to be reached and may make it possible to obtain pregnancies.

Ovarian stimulation drugs alter the metabolite content of the growing follicle: in vivo spectroscopic evaluation of follicle fluid

Objective: To determine and compare metabolite content using magnetic resonance spectroscopy (MRS) of growing follicles in patients with polycystic ovary syndrome (PCOS) receiving recombinant follicle stimulating hormone (rFSH), clomiphene citrate (CC) or aromatase inhibitor (AI) for ovarian stimulation. Material and Methods: Thirty patients diagnosed with PCOS and infertility and scheduled for ovarian stimulation were divided by therapy, rFSH/CC/AI, into three equal groups. Five fertile cases were designated as the control group. When the follicle diameters reached 16-18 mm in each group, patients underwent MRS and the metabolite content of a dominant follicle was analyzed. N-acetylaspartate, lactate (Lac), creatine (Cr), and choline (Cho) metabolite levels in parts per million were measured in the spectra. Results: A ~three-fold decrease in dominant follicle Cho content was found in patients receiving CC compared to control subjects. Similarly, the dominant follicle Cho intensities of patients given rFSH and AI were noted to be significantly higher than those who received CC. Only dominant follicle Lac levels of the patients who received CC were found to be significantly higher than the other groups. Cr peak intensities of patients receiving CC were found to be approximately three times less than control subjects. Cr signal intensity was significantly higher in patients receiving rFSH or AI than in patients receiving CC. While two patients became pregnant in the CC group, three patients in the AI group and five patients in the rFSH group became pregnant. The main metabolites detected in patients who conceived in each group were Cho and Cr. In cases who could not conceive, while Lac and lipid signals increased, Cho and Cr signals decreased. Conclusion: Unlike CC, ovarian stimulation with rFSH or AI does not alter dominant follicle metabolite content. The developmental capacity of a growing egg may be determined non-invasively with MRS.

Prolonged luteal phase support with progesterone may increase papules and plaques of pregnancy frequency in pregnancies through in vitro fertilization.

BACKGROUND: Pruritic urticarial papules and plaques of pregnancy development may have a strong relationship with hormone treatments during in vitro fertilization and hormonal changes during pregnancy. OBJECTIVES: The aim of this study was to evaluate and compare the frequency of papules and plaques of pregnancy and related factors in in vitro fertilization pregnancies and spontaneous pregnancies. METHODS: In this study, 517 in vitro fertilization pregnancies and 1253 spontaneous pregnancies were retrospectively reviewed for papules and plaques of pregnancy frequency. The diagnosis of papules and plaques of pregnancy was performed by referral to the dermatology department and according to the typical clinical manifestations of the disease. RESULTS: The papules and plaques of pregnancy was more common in all in vitro fertilization pregnancies (including single pregnancies) than in spontaneous pregnancies. Age, Rh positivity, mother weight gain, onset of disease during gestation, duration of disease, birth weight and the frequency of male fetus were similar between the two groups (p>0.05). The rate of multiple pregnancies was higher in in vitro fertilization pregnancies with papules and plaques of pregnancy than in vitro fertilization pregnancies without papules and plaques of pregnancy (p<0.001). Duration of progesterone treatment was also significantly longer in in vitro fertilization pregnancies with papules and plaques of pregnancy compared to in vitro fertilization pregnancies without papules and plaques of pregnancy (p<0.001). STUDY LIMITATIONS: The limitations of the study were the retrospective and single-centered design. CONCLUSION: The results of this study indicate that increased progesterone dosage or prolonged treatment may play a role in the pathogenesis papules and plaques of pregnancy.

Frozen embryo transfer prevents the detrimental effect of high estrogen on endometrium receptivity.

OBJECTIVE: To investigate whether serum levels of estradiol affect reproductive outcomes of normoresponder women undergoing fresh embryo transfer (ET) versus frozen-thawed ET (FET). MATERIAL AND METHODS: Two hundred fifty-five normoresponder women underwent fresh ET in their first or second in vitro fertilization cycle. Ninety-two women with negative pregnacy test results underwent FET. Clinical and ongoing pregnancy rates, implantation, and live birth rates of women undergoing fresh ET versus FET were compared. RESULTS: One hundred forty-seven (57.65%) out of the 255 normoresponder women receiving FET had positive beta-human chorionic gonadotrophin (hCG) results. The remaining 108 women had negative beta-hCG results. The clinical pregnancy rates of the fresh ET group were found as 55.69% (n=142). Ninety-two of the 108 women with failed pregnancies underwent FET; 72.83% had positive beta-hCG results (n=67), and 70.65% had clinical pregnancy (n=65). Both biochemical and clinical pregnancy rates of women undergoing FET increased significantly (p<0.012 and p<0.013, respectively). Ongoing pregnancy (60.87% vs. 52.94%) and live birth rates (59.87% vs. 48.63%) were similar in both fresh and FET groups. Serum E2 levels of women who failed to conceive were significantly higher than those women did conceive. Serum progesterone levels of women who conceived versus those that did not were similar. CONCLUSION: The detrimental effect of high serum estradiol levels on endometrial receptivity could be prevented by FET.

Prolonged luteal phase support with progesterone may increase papules and plaques of pregnancy frequency in pregnancies through in vitro fertilization

Abstract Background: Pruritic urticarial papules and plaques of pregnancy development may have a strong relationship with hormone treatments during in vitro fertilization and hormonal changes during pregnancy. Objectives: The aim of this study was to evaluate and compare the frequency of papules and plaques of pregnancy and related factors in in vitro fertilization pregnancies and spontaneous pregnancies. Methods: In this study, 517 in vitro fertilization pregnancies and 1253 spontaneous pregnancies were retrospectively reviewed for papules and plaques of pregnancy frequency. The diagnosis of papules and plaques of pregnancy was performed by referral to the dermatology department and according to the typical clinical manifestations of the disease. Results: The papules and plaques of pregnancy was more common in all in vitro fertilization pregnancies (including single pregnancies) than in spontaneous pregnancies. Age, Rh positivity, mother weight gain, onset of disease during gestation, duration of disease, birth weight and the frequency of male fetus were similar between the two groups (p > 0.05). The rate of multiple pregnancies was higher in in vitro fertilization pregnancies with papules and plaques of pregnancy than in vitro fertilization pregnancies without papules and plaques of pregnancy (p < 0.001). Duration of progesterone treatment was also significantly longer in in vitro fertilization pregnancies with papules and plaques of pregnancy compared to in vitro fertilization pregnancies without papules and plaques of pregnancy (p < 0.001). Study limitations: The limitations of the study were the retrospective and single-centered design. Conclusion: The results of this study indicate that increased progesterone dosage or prolonged treatment may play a role in the pathogenesis papules and plaques of pregnancy.