Proposal for Diagnostic Criteria of Y-Shaped Dysmorphic Uterus Based on 3-Dimensional Transvaginal Ultrasound Measurements.

STUDY OBJECTIVE: To define objective and readily applied diagnostic criteria for Y-shaped uteri using 3-dimensional transvaginal ultrasound (3D-TVUS) volume recordings. DESIGN: A retrospective case-control diagnostic measurements study. SETTING: A tertiary university hospital's reproductive health and research center. PATIENTS: Two hundred thirteen patients who presented with infertility between January 2020 and December 2022. INTERVENTIONS: Two blinded physicians re-evaluated the 3D-TVUS images of all patients for the presence of a uterine abnormality. The images of patients with a Y-shaped uterus were re-evaluated, and descriptive measurements were done. MEASUREMENTS AND MAIN RESULTS: The most common uterine abnormality in this cohort was the Y-shaped uterus with a prevalence of 12.2%, followed by the arcuate, T-shaped, and septate uteri, respectively. Reviewers identified 26 and 28 Y-shaped uteri, respectively, and came to a consensus on 25 images. Diagnostic criteria for the Y-shaped uterus based on 3D-TVUS findings have been specified as: lateral indentation depths between 4 and 7 mm, fundal indentation depth between 5 and 9 mm, lateral indentation angles between 121° and 149°, fundal indentation angle between 121° and 145°, and Y-angles 25° to 46°. CONCLUSION: Some subtypes of dysmorphic uteri, such as the Y-shaped uterus, whose clinical significance is unknown and may be variants of the normal, may actually be more common than thought. Determining objective diagnostic criteria with 3D-TVUS will allow standard research on these anomalies and their clinical significance.

Evaluation of the Impact of Letrozole in Combination with the GnRH Antagonist Ovarian Stimulation Protocol in Patients Expected to Have a Poor Ovarian Response (POSEIDON Groups 3 and 4).

Background and Objectives: The objective of this study was to evaluate the impact of adjuvant letrozole administration during ovarian stimulation using the gonadotropin-releasing hormone (GnRH) antagonist protocol on treatment outcomes in women categorized into POSEIDON groups 3 and 4. Materials and Methods: This retrospective cohort study analyzed data from patients classified into POSEIDON groups 3 and 4 who underwent fresh embryo transfer subsequent to intracytoplasmic sperm injection following a GnRH antagonist stimulation protocol between January 2017 and December 2021. Patients were divided into two groups: the GnRH-LZ group, who received letrozole at a dosage of 5 mg/day for five consecutive days, and the GnRH-ant group, who did not receive adjuvant letrozole. The primary outcome measure of the study was a comparative analysis of live birth rates between the two groups. Results: A total of 449 patients were deemed suitable for final analysis and were allocated into two groups: 281 patients in the GnRH-ant group and 168 patients in the GnRH-LZ group. Live birth rates were found to be comparable in both groups (11% vs. 9%, p = 0.497). Letrozole administration significantly reduced the total amount of gonadotropins required (2606.2 ± 1284.5 vs. 3097.8 ± 1073.3, p < 0.001), the duration of ovarian stimulation (11.2 ± 3.9 vs. 10.2 ± 3, p = 0.005), and the serum peak estradiol concentration (901.4 ± 599.6 vs. 463.8 ± 312.3, p < 0.001). Conclusions: Adjuvant letrozole administration did not demonstrate a significant impact on live birth rates among women categorized into POSEIDON groups 3 and 4. However, this approach may offer potential cost reductions by diminishing the necessity for exogenous gonadotropins and shortening the duration of ovarian stimulation.

Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: a case series.

BACKGROUND: With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias. OBJECTIVE: This study aimed to investigate the safety of performing autologous ovarian tissue transplantation in survivors of acute leukemia. STUDY DESIGN: Clinical, histopathological, and molecular data of 4 women with acute myeloid leukemia and 2 women with acute lymphoblastic leukemia who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66% to 100% of an ovarian cortex with a slow freezing method, all women received high-dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Before the ovarian tissue transplantation, (1) antral follicle counts, serum antimüllerian hormone and follicle-stimulating hormone levels were assessed to confirm primary ovarian insufficiency; (2) all recipients were cleared by their hematologist-oncologists; (3) representative cortical strips were screened for leukemia infiltration by histologic (hematoxylin and eosin staining), immunohistochemical (CD3, CD20, CD34, CD68, CD117, CD163, PAX-5, Tdt, lysozyme, and MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate. RESULTS: The median age was 20 years (interquartile range, 15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction or consolidation chemotherapy that included cytarabine + daunorubicin or Berlin-Frankfurt-Munich-95 protocol and were in remission. The mean serum antimüllerian hormone was 1.9±1.7 ng/mL before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (interquartile range, 41-120) after ovarian tissue cryopreservation. Ovarian function resumed in all patients after a median of 3.0 months (range, 2.5-4.0), and 2 women had 1 live birth each. The median graft longevity was 35.5 months (interquartile range, 18-57) after ovarian tissue transplantation. After a median follow-up of 51 months (interquartile range, 20-74), all patients remained relapse-free. In 1 patient, the graft was removed during cesarean delivery and was negative for immunochemical leukemia markers. CONCLUSION: Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by nongonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy before allogeneic hematopoietic stem cell transplantation.

Random start ovarian stimulation before gonadotoxic therapies in women with cancer: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.

Cord blood anti-Müllerian hormone levels are higher in female newborns from women with polycystic ovary syndrome (PCOS) when compared to non-PCOS controls, irrespective of body mass index; a prospective case-control study.

OBJECTIVE: To compare cord-blood anti-Müllerian hormone levels between female newborns from women with and without polycystic ovary syndrome. METHODS: A prospective case-control study was conducted in Ankara University School of Medicine, Department of Obstetrics and Gynecology between June 2020 and January 2021. In total, 408 women gave birth to a female during the study period. Of those, 45 had a polycystic ovary syndrome-like history. We did not find the preconceptional history of 16 women. Two women were excluded due to other endocrine disorders. The polycystic ovary syndrome group consisted of 27 women with polycystic ovary syndrome that gave birth to a female newborn during the study period and the non-polycystic ovary syndrome control group consisted of 33 women who had regular cycles prior to pregnancy, were never diagnosed with polycystic ovary syndrome, and gave birth to female newborns. The primary outcome measure was the cord-blood anti-Müllerian hormone levels. RESULTS: The median cord-blood anti-Müllerian hormone levels of female newborns from polycystic ovary syndrome patients were significantly higher than those in the non-polycystic ovary syndrome group (0.33ng/ml vs. 0.12ng/ml, respectively; p<0.001). In addition, cord blood anti-Müllerian hormone levels were significantly higher in both obese and non-obese polycystic ovary syndrome patients when compared to body-mass-index-matched non- polycystic ovary syndrome patients (0.37ng/ml vs. 0.06ng/ml, respectively; p=0.013 and 0.30ng/ml vs. 0.11 ng/ml, respectively; p=0.003). CONCLUSIONS: The cord blood anti-Müllerian hormone levels were higher in female newborns of women with polycystic ovary syndrome when compared to non-polycystic ovary syndrome controls. The effect of polycystic ovary syndrome seems to be greater than body mass index on cord blood anti-Müllerian hormone levels.

The size, number and bilaterality of endometriomas do not affect spontaneous conception chance following surgical removal.

OBJECTIVE: Endometrioma surgery is associated with a reduction in ovarian reserve. However, removal of an endometrioma may increase the likelihood of a spontaneous conception. The objective of this study was to assess the pre-operative and operative variables affecting spontaneous conception following endometrioma surgery. METHODS: Data from 211 women ≤40 years of age who underwent an endometrioma surgery at a university-based infertility clinic between January 2005 and June 2020 were reviewed retrospectively. The main outcome measure was spontaneous clinical pregnancy. We had 84 women with and 127 women without a successful spontaneous conception making up the case and control groups. RESULTS: The median ages of the cases and controls were 27 and 32 years, respectively (p<0.001). The rate of recurrence was significantly lower in the spontaneous conception group when compared to controls (29.8% vs. 52.8%, respectively; p=0.001). Our results showed no differences in the number, size, or side of the endometriomas in both groups. Multivariate logistic regression analysis showed significant independent effects of age (B: -.166, OR {odds ratio}: 0.847, 95% CI {confidence interval}: 0.791-0.907, p<0.001), recurrence (B: -1.030, OR: 0.357, 95% CI: 0.188-0.678, p=0.002), and laparoscopic surgery rather than laparotomy (B: 1.585, OR: 4.879, 95% CI: 1.029-23.133, p=0.046) for spontaneous conception. CONCLUSIONS: The size, number and bilaterality of the endometrioma did not affect the spontaneous conception likelihood following surgical removal. However, increasing age and recurrence are negatively associated with the likelihood of spontaneous conception. Laparoscopic surgery may increase the chance of spontaneous conception when compared to laparotomy.

A Holistic Approach To Oncofertility In A Patient With Rectal Cancer: A Case Report.

OBJECTIVE: Cryopreservation techniques are used to preserve fertility before cancer treatment with gonadotoxic agents. Herein, we report a case of fertility preservation involving a 29-year-old G0P0 woman, married for one year, who was referred to our hospital for fertility preservation before starting rectal cancer treatment. CASE DESCRIPTION: Ovarian tissue and embryo cryopreservation were performed. Before the procedure, ovarian reserve was evaluated, and antral follicle counts were determined. Laparoscopic ovarian tissue cryopreservation was performed from the left side with a lower antral follicle count. Thus, we were able to keep the number of oocytes obtained in the following controlled ovarian hyperstimulation cycle at the highest level. Subsequently, the right ovary was transposed into the lateral wall of the abdomen under the peritoneum. Conventionally controlled ovarian hyperstimulation was initiated on the first postoperative day, depending on the menstrual cycle phase. Intracytoplasmic sperm injection was performed on four mature oocytes obtained, and one embryo was cryopreserved. Controlled ovarian hyperstimulation was initiated on the first postoperative day, and the process was repeated on the seventh postoperative day, yielding a total of seven viable embryos for cryopreservation. CONCLUSIONS: There is usually only one chance of controlled ovarian hyperstimulation in patients requiring a fertility-sparing approach due to malignancy. In the combined technique, performing ovarian tissue resection from the ovary with a lower number of antral follicles can keep the number of oocytes at the highest level in the following controlled ovarian hyperstimulation cycle.

Transabdominal ultrasound-guided oocyte retrieval for oocyte cryopreservation using a vaginal probe: a comparison of applicability, effectiveness, and safety with conventional transvaginal approach.

PURPOSE: We aimed to compare the feasibility, effectiveness, and safety of transabdominal ultrasound-guided oocyte retrieval (TUGOR) using a vaginal probe and traditional vaginal approach in virgin patients undergoing oocyte cryopreservation. METHODS: A total of 116 virgin patients who underwent transabdominal ultrasound-guided oocyte retrieval using a vaginal ultrasound probe and 33 patients matched for BMI, antral follicle count, age, day 3 FSH, estradiol, and AMH who underwent vaginal approach were enrolled. Mean number of total oocytes collected, mean number of cryopreserved MII oocytes, duration of the procedure, duration of stimulation, mean gonadotropin consumption, mature oocyte ratio, and a modified follicle-oocyte index were compared between the groups. RESULTS: No statistical difference was found between the groups in mean number of follicles > 12 mm (4.62 ± 4.54 vs. 5.44 ± 4.52), mean number of oocytes collected (4.44 ± 4.14 vs. 5.33 ± 4.52), mean number of cryopreserved MII oocytes (4.01 ± 3.67 vs. 4.53 ± 4.13), mean duration of the procedure (12.4 ± 1.2 vs. 13.4 ± 1.6 min), mean days of stimulation (8.05 ± 1.91 vs. 8.35 ± 1.72 days), mean gonadotropin consumption (1507.9 ± 475.3 vs. 1571.74 ± 404.6 units), mature oocyte ratio (0.78 ± 0.24 vs. 0.82 ± 0.26), and modified follicle oocyte index (0.86 ± 0.63 vs. 0.84 ± 0.19). In the TUGOR group, superficial epigastric artery injury occurred in two patients and resolved spontaneously. CONCLUSION: Transabdominal oocyte retrieval using a vaginal ultrasound is a safe, effective, and feasible method of oocyte retrieval in some selected patient groups.

Laparoscopy versus open surgery for the surgical management of tubo-ovarian abscess (TOA). Is there a beneficial impact of early endoscopic intervention in terms of fertility rates?

OBJECTIVES: To compare success rates and complications in women undergoing laparoscopic versus open surgical management of tubo-ovarian abscess. We further examined whether early laparoscopic intervention has any impact on pregnancy rates in a subgroup of infertile patients following frozen-thawed embryo transfer. MATERIAL AND METHODS: Hospital records of 48 patients diagnosed with TOA between January 2015 and December 2020, who underwent surgical intervention or received only medical treatment were analyzed. All patients were hospitalized, and parenteral antibiotics were commenced on admission initially. Laparoscopic or open surgery was performed within 48 hours course of intravenous antibiotherapy (early intervention) or later according to the clinical findings and antibiotherapy response. RESULTS: Of 48 patients with TOA, 18 (37.5%) underwent laparoscopic and 30 (62.5%) underwent open surgical intervention. The median postoperative hospital stay was shorter (4.5 days vs 7.5 days, respectively; p = 0.035), and postoperative opioid analgesic requirement was lesser in the laparoscopy group compared to open surgery group (22% vs 53%, respectively; p = 0.034). Intra- and post-operative complication rates were similar between the groups. Of these 48 patients, seven were diagnosed to have TOA following oocyte retrieval, and four of these conceived with frozen thawed embryo transfer all of whom underwent laparoscopic surgery within 48 hours of diagnosis. CONCLUSIONS: Minimal invasive surgery should be preferred even in the presence of severely adhesive and inflammatory TOA in order to improve postoperative outcomes. Moreover, early laparoscopic intervention may be considered in infertile patients with an aim to optimize pregnancy rates in a subsequent frozen-thawed embryo transfer.

Presence of Endometrioma Does Not Impair Embryo Quality and Assisted Reproductive Technology (ART) Cycle Outcome in Diminished Ovarian Reserve (DOR) Patients.

This study aims to assess the impact of endometrioma on embryo quality and cycle outcome in patients who undergo assisted reproductive technology (ART) treatment due to diminished ovarian reserve (DOR). Retrospective case-control study was conducted in women ≤ 40 years of age who underwent ART treatment caused by DOR, defined according to POSEIDON criteria, at a university-based infertility clinic between January 2015 and December 2020. Three groups of patients were selected: group A included patients with an idiopathic DOR, group B included patients with endometrioma(s) who underwent ovarian cystectomy, and group C included patients with endometrioma(s) without surgical treatment. A total of 351 women with DOR were included in the final analysis. Demographic characteristics, including age and AMH, were similar between the groups. Significant differences were observed among groups on mean number of MII oocytes retrieved (1.88 ± 1.59 vs. 2.84 ± 2.89 vs. 2.78 ± 2.41, respectively; p < 0.001) and mean number of embryos (1.04 ± 1.18 vs. 1.87 ± 2.01 vs. 1.66 ± 1.81, respectively; p < 0.001). However, the mean number of top-quality embryos, cycle cancellation, and live birth rates were similar between the groups. Clinical pregnancy (35 (26.5%) vs. 8 (18.2%) vs. 18 (42.9%), respectively; p = 0.038) and miscarriage rates (12 (9.1%) vs. 0 vs. 8 (19.0%), respectively; p = 0.009) were higher in endometrioma group without surgery. Women with DOR appear to have similar ART cycle outcomes regardless of the etiology, in terms of live birth rates. Infertility of endometrioma patients might be related to altered endometrium rather than to decreased oocyte quality. Cystectomy for endometrioma before IVF did not seem to affect the LBR.

Impact of an estrogen replacement regimen on live birth rate in frozen-thawed good-quality embryo transfer.

OBJECTIVE: To assess the impact of an estrogen replacement regimen on frozen embryo transfer (FET) cycle outcome. METHODS: In the present retrospective cohort study, data of infertile women undergoing FET with good-quality embryos were reviewed. The first group received 2 mg of estradiol hemihydrate (EH) once daily for 6 to 7 days, then twice daily for 4 to 5 days, and then three times a day until embryo transfer. The second group received EH twice daily for 7 to 8 days, then three times a day. The third group received EH three times a day constantly. The main outcome measure was live birth rate. RESULTS: In total, 394 FET cycles were included. The fixed 6-mg group required the highest estradiol hemihydrate dose. The duration of estrogen treatment was significantly longer in the first group. Maximal endometrial thickness was highest in the second group (10.2 ± 1.3 mm vs. 9.6 ± 1.4 mm vs. 8.6 ± 0.9 mm, respectively; P < 0.001). The clinical pregnancy rates in the groups were 41.1%, 55.2%, and 42.2%, respectively (P = 0.035). Live birth rates were 40.8%, 50.9%, and 48.1%, respectively (P = 0.320). CONCLUSION: In FET cycles with hormone replacement therapy, a step-up 4-mg regimen provides thicker endometrium with optimal-dose estrogen in an adequate time frame. The tendency for increased clinical pregnancy and live birth rates is remarkable.

Endometrial compaction is associated with the increased live birth rate in artificial frozen-thawed embryo transfer cycles.

We aimed to assess the effect of endometrial compaction on the live birth rate in frozen-thawed embryo transfer (FET) cycles and to investigate the parameters associated with compaction. FET cycles performed in a tertiary care infertility centre between May 2013 and October 2019 were reviewed retrospectively. The decremental change of endometrial thickness between the end of oestrogen phase and ET day was defined as endometrial compaction. The primary outcome measure was endometrial compaction, and the secondary outcome was the live birth rate. Among all, 89 had endometrial compaction and 194 did not. The live birth rate was significantly higher in the compaction group (23.6 vs. 13.4%, respectively; p = 0.039). Multivariate logistic regression analysis revealed that in FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction [OR: 3.133, 95% confidence interval (CI) 1.104-8.892; p = 0.032] when adjusted for age, stage of the embryo, and endometrial thickness at the end of the oestrogen phase. According to receiver operating characteristic (ROC) curve analysis the sensitivity and specificity of 9.25 mm endometrial thickness at the end of oestrogen phase were 76.4 and 58.8%, respectively (area under the curve: 0.701, 95% CI 0.640-0.763; p < 0.001) to predict endometrial compaction.

Longitudinal change in serum inflammatory markers in women with tubo-ovarian abscess after successful surgical treatment: a retrospective study.

High levels of serum inflammatory markers are related to extended hospitalisation and more severe disease in the case of tubo-ovarian abscess (TOA). There is scarce information on the serial measurement of inflammatory markers during the postoperative follow-up period of surgically treated TOA. The present study aimed to assess the postoperative longitudinal changes in serum inflammatory markers following surgery for TOA. In this retrospective cohort study, patients who underwent surgery for TOA between January 2010 and March 2020 were reviewed. All inflammatory markers peaked within 48 hours after surgical intervention and then declined with time. The predicted mean of white blood cell count (WBC) to return to normal was 2.5 days (95% CI: 1.0-4.3), which was followed by neutrophil to lymphocyte ratio (NLR) (7.1 days, 95% CI: 4.7-10.8) and C-reactive protein (CRP) (+14 days). In conclusion, serum inflammatory markers increase in the very early post-operative period. While the normalisation period is very slow, it may not be appropriate to use CRP for evaluating the treatment success of TOA surgery. However, WBC and NLR measurements might be useful for follow-up and predicting the need for medical or surgical intervention.Impact statementWhat is already known on this subject? Serum inflammatory markers such as C-reactive protein, white blood cell count, and neutrophil to lymphocyte ratio are usually elevated in women with tubo-ovairan abscess, and high levels of these markers are associated with extended hospitalisation and more severe disease.What do the results of this study add? Our results indicate that the serum inflammatory markers increase and peak within the first 48 hours after surgery for tubo-ovarian abscess. Normalisation of white blood cell count is the fastest in successfully treated patients. However, normalisation of C-reactive protein is slowest, reaching 14 days and might not be as feasible as white blood cell count and neutrophil to lymphocyte ratio in postoperative patient follow-up.What are the implications of these findings for clinical practice and further research? The serum inflammatory markers should be interpreted with caution within 48 hours after surgical treatment for tubo-ovarian abscess. Instead of C-reactive protein white blood cell count, and neutrophil to lymphocyte ratio measurements can be preferred in post-operative follow-up to predict the need for further medical or surgical intervention.

Intrauterine insemination with ovarian stimulation is a successful step prior to assisted reproductive technology for couples with unexplained infertility.

The present retrospective cohort study analysed data of couples with unexplained infertility who underwent two to three intrauterine insemination (IUI) cycles. The inclusion criteria were age 20-40 years, failure to conceive for at least two years of unprotected intercourse, ovulation, normal semen analysis, and tubal patency. Total of 578 IUI cycles of 286 couples with unexplained infertility were included in the final analyses. The mean age and duration of infertility of the study population were 28.8 ± 5.1 and 5.2 ± 3.4 years, respectively. The clinical pregnancy rate (CPR) and live birth rate (LBR) per cycle were 16.6 and 13.1%, respectively. The cumulative CPR following two to three IUI cycles was 33.5% and the cumulative LBR was 26.5% for the entire cohort. The duration of infertility was significantly shorter in women whose IUI attempt were successful (p = .036). Up to three cycles of IUI with ovarian stimulation seems as an effective first-line treatment modality in unexplained infertility.IMPACT STATEMENTWhat is already known on this subject? Cont rolled ovarian stimulation combined with intrauterine insemination (IUI) is a common infertility treatment as a low-cost, less-invasive alternative to in vitro fertilisation (IVF) and was approved as a first line treatment option for unexplained infertility However, the UK National Institute for Health and Care Excellence (NICE) guideline states that IUI is not recommended to couples with unexplained infertility, male factor and mild endometriosis, unless the couples have religious, cultural or social objections to proceed with IVF.What do the results of this study add? Up to three IUI cycles with ovarian stimulation can be considered as an effective treatment modality in unexplained infertility even in couples who could not achieve pregnancy by expectant management for two years.What are the implications of these findings for clinical practice and/or further research? The clinicians should reconsider the NICE recommendation of IVF in the light of recent studies including ours which recommend IUI together when dealing couples with unexplained infertility.

A Feasible Option before Cycle Cancellation for Poor Responders; STOP-START Protocol.

Despite the advances in controlled ovarian stimulation (COS), management of a subgroup of poor ovarian responder patients may still be challenging. We describe a feasible and simplified protocol, namely the STOP-START protocol, for poor responders defined as Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) groups 3 and 4, who are unresponsive to COS with maximum dose gonadotrophins. Data of 11 women unresponsive to COS were reviewed. Mean age of the patients was 36.5 ± 6.0 years. Unresponsiveness was defined as no follicular growth >9 mm and/or estradiol level less than 40 pg/ml after a week of recombinant follicle stimulating hormone (rFSH, 225-300 IU) administration. In that case, COS was stopped and each woman underwent weekly ultrasound assessment to catch a secondary follicular growth. All women showed at least one follicular growth within five to 20 days. Six women (54.5%) had spontaneous follicular growth and the other five required ovarian stimulation. At least one oocyte was retrieved from each one of seven patients (63.6%). The mean number of oocytes retrieved was 1.6 ± 1.4 and five women (45.5%) had at least one grade A embryo. Among all, two women became pregnant successfully and both gave live births (18.2%). In conclusion, STOP-START protocol may potentially be an effective, feasible, and time-saving management option for POSEIDON group 3/4 poor responders who are unresponsive to standard COS treatment with maximum dose gonadotrophins.

Combined Fertility Preservation Technique before Gonadotoxic Treatments in Cancer Patients.

Although ovarian tissue cryopreservation is still considered as an experimental technique, several authors from around the world have reported successful and promising results. Currently, oocyte cryopreservation seems to be the most feasible technique for fertility preservation when there's some kind of a time constraint in adolescents and adults. However, it has been estimated that a young woman would be expected to have a 94% likelihood of having a live birth with 20 mature frozen oocytes (1). At age 34 years, however, this expectation is decreased to 90% with 20 mature frozen oocytes. In addition to age-related limitations, an immediate obstacle for obtaining oocytes in cancer patients is the fact that only one controlled ovarian hyperstimulation (COH) cycle can usually be performed in these women because of time constraints, yielding a relatively low number of oocytes and/or embryos. For this reason, results from egg donation programs cannot be extrapolated to cancer patients, nor can the quality of oocytes be guaranteed. Hence, a combined fertility preservation technique can be of valuable in increasing the chances of successful future pregnancies following gonadotoxic cancer therapies. Previously, Dolmans et al. (2) suggested that cryopreservation of bilateral ovarian cortex followed by COH is a feasible and safe approach to preserve fertility before gonadotoxic treatment, and that the number of cryopreserved embryos was similar to the controls. We have been offering the option of the combined technique to fertility preservation patients for a couple of years and have performed it in a series of eight candidate patients. All patients had enough time for COH before oncology treatments. We first performed laparoscopic ovarian resection for ovarian tissue cryopreservation and then started COH on postoperative day 0 or 1 in each patient (Table 1). The main point in our findings is that ovarian resection is performed from the side with less antral follicle count of the patients. We suggest that this approach can increase the oocyte yield in a single available COH cycle. The data is limited on the effectiveness of combined technique and more long-term follow-up studies are needed in larger groups with appropriate controls. According to our clinical experience, we believe that combined technique is a valid approach, which is expanding beyond the experimental stage and has become a clinical technique for fertility preservation. We particularly suggest selecting the ovary with a low antral follicle count for wedge resection to increase oocyte yield. The information gathered from large international multicenter reports would encourage physicians to agree that the method should complete the experimental phase and be ready for wider clinical use in female fertility preservation.

Anorexigenic peptide (leptin, obestatin, nesfatin-1) levels and their impact on assisted reproductive technology treatment outcomes in patients with polycystic ovary syndrome.

OBJECTIVE: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. METHODS: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. RESULTS: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. CONCLUSION: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

Factors associated with livebirth in couples undergoing their first in vitro fertilization cycle: An internally validated prediction model

Objective: The aim of the study is to create a new model to predict successful outcome in assisted reproductive techniques. Materials and Methods: A retrospective cohort study was conducted in tertiary fertility center between 2010 and 2017. Nulliparous women younger than 45 years-old undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for the first time were included; frozen embryo transfers, canceled induction cycles, freeze-all cycles were excluded. Two prediction models were built using multivariate logistic regression with a subset of the dataset and then were internally validated using bootstrapping methods. Results: Four hundred eighty eight women were included with 136 (27.9%) live births. The basal model was built using variable age, antral follicle count (AFC), and basal luteinizing hormone (LH) levels. Age over 37 years [odds ratio (OR): 0.07, 95% confidence interval (CI): 0.00-0.36] and AFC below 5 (OR: 0.15, 95% CI: 0.02-0.53) was associated with poorer outcomes whereas an LH level above 6 mIU/mL (OR: 2.24, 95% CI: 1.27-3.94) was associated with better outcomes. Optimism adjusted area under the curve (AUC) of this model was 0.68 (95% CI: 0.62-0.74). Combined model in addition to basal model variables included the length of induction cycle, the endometrial thickness at the day of transfer, grade and count of the transferred embryo. Cycles lasting more than ten days (OR: 2.23, 95% CI: 1.17-4.42), an endometrial thickness greater than 9 mm (OR: 2.07, 95% CI: 1.00-4.53) were associated with better outcomes. Optimism adjusted AUC of this model was 0.76 (95% CI: 0.70-0.81). Calibration of both models was good according to Hosmer Lemeshow test (p=0.979 and p=0.848, respectively). Conclusion: This internally validated prediction model has good calibration and can be used predicting outcomes in first time IVF/ICSI cycles with modest sensitivity.

hCG day progesterone level has no impact on the frozen thawed embryo transfer cycle outcome.

OBJECTIVE: To assess the association between hCG day progesterone levels and subsequent frozen-thawed embryo transfer (FET) cycle outcome in infertile women with and without polycystic ovary syndrome (PCOS). METHOD: Data of 178 women who underwent FET at a university-based infertility clinic between January 2016 and December 2019 were reviewed. The study group consisted of women who had progesterone elevation (PE) during fresh controlled ovarian stimulation (COS) cycle. A sub-group analysis was also performed in PCOS and non-PCOS patients. RESULTS: There were no differences in clinical pregnancy (47.7 % vs. 50.7 %, p = 0.729), miscarriage (15.9 % vs. 22.4 %, p = 0.359), and live birth rates (27.3 % vs. 23.9 %, p = 0.652) following FET between women with and without PE in the fresh cycle. The results remained non-significant regarding the clinical pregnancy (46.7 % vs. 53.4 %, p = 0.549), miscarriage (13.3 % vs. 27.6 %, p = 0.133), and live birth rates (26.7 % vs. 19.0 %, p = 0.408) in participants with PCOS (n = 88). CONCLUSION: hCG day progesterone level in the fresh COS cycle does not have a significant impact on the subsequent FET cycle neither in PCOS nor in non-PCOS women.

Clomiphene Citrate versus Recombinant FSH in intrauterine insemination cycles with mono- or bi-follicular development.

OBJECTIVE: The present study aims to assess the success of controlled ovarian stimulation in intrauterine insemination cycles stimulated by recombinant-FSH and Clomiphene citrate for either mono- or bi-follicular development. METHODS: We assessed 870 infertile patients treated with controlled ovarian stimulation in intrauterine insemination cycles at a university-based infertility clinic between January 2012 and December 2017. We compared the cycles stimulated by clomiphene citrate and recombinant-FSH in two set-ups; mono- and bi-follicular development. The main outcome measure was the clinical pregnancy rate per cycle. RESULTS: The demographic and cycle parameters were similar between the groups, except for endometrial thickness on the day of hCG administration, which was higher in the recombinant-FSH group than the clomiphene citrate group. The overall clinical pregnancy rates in clomiphene citrate and recombinant-FSH groups were 9.8% and 10.3%, respectively (p=0.940). Regarding the entire cohort, clinical pregnancy was significantly higher in cases of bi-follicular development when compared to mono-follicular development (16.8% vs. 10.2%, respectively; p=0.009). CONCLUSIONS: Clomiphene citrate and recombinant-FSH have similar success rates in terms of clinical pregnancy, in either mono-follicular development or bi-follicular development. Clomiphene citrate and recombinant-FSH cycles resulted in comparable rates of bi-follicular development, which significantly increases clinical pregnancy rate. Clomiphene citrate and recombinant-FSH have similar success rates in terms of clinical pregnancy, in either mono-follicular development or bi-follicular development.