Ezgi Demirtas

Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients

As cancer treatment outcomes improve, the number of women with cancer seeking fertility preservation increases. Currently, embryo/oocyte cryopreservation appears to provide the best fertility preservation option. However, patients may not have sufficient time to undergo ovarian stimulation prior to chemotherapy and/or the hormones used in ovarian stimulation are contraindicated for certain tumours. In-vitro maturation has been suggested as an effective treatment for these patients. This report presents three women aged 21, 30 and 40 years, without male partners, seeking fertility preservation prior to chemotherapy. They were first seen during the luteal phase of their menstrual cycle and were to undergo gonadotoxic treatment imminently. They underwent immature oocyte retrieval in the luteal phase and seven, five and seven immature oocytes were recovered, respectively. After in-vitro maturation, five, three and five metaphase II (MII) oocytes were vitrified. Two patients later underwent one and two more retrievals, respectively, in the follicular phase of the next cycle(s) and additional oocytes were cryopreserved. These results suggest that immature oocytes recovered in the luteal phase can successfully be matured in vitro; therefore, if there is not sufficient time for conventional follicular-phase oocyte retrieval in a stimulated/unstimulated cycle prior to chemotherapy, a retrieval in the luteal phase could be considered.

A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles.

BACKGROUND Our aim was to evaluate whether extending the interval between human chorionic gonadotrophin (hCG) priming and immature oocyte retrieval increases the oocyte maturation rate following in vitro maturation (IVM). METHODS This study was performed retrospectively. IVM was performed on 113 polycystic ovary syndrome patients (n = 120 cycles). Oocyte collection was performed either 35 h (Group 1; n = 76) or 38 h (Group 2; n = 44) after 10 000 IU of hCG priming. Following oocyte retrieval, oocyte maturity was assessed and the remaining immature oocytes were cultured in IVM medium up to Day 2. RESULTS The number of in vivo matured oocytes collected was significantly higher in Group 2 (13.6%, 114/840 versus 7.3%, 96/1312 in Group 1) (P < 0.01); the oocyte maturation rate after Day 1 was significantly higher (P < 0.01) in Group 2 (46.3 versus 36.0% in Group 1); and clinical pregnancy (40.9 versus 25%) and implantation rates (15.6 versus 9.6%) were better in Group 2 than those in Group 1. CONCLUSIONS The results suggest that extending the period of hCG priming time from 35 to 38 h for immature oocyte retrieval promotes oocyte maturation in vivo and increases the IVM rate of immature oocytes. Therefore, oocyte retrieval after 38 h of hCG priming may improve subsequent pregnancy outcome in cycles programmed for IVM treatment.

Comparison of in-vitro maturation cycles with and without in-vivo matured oocytes retrieved

This study compared the embryological characteristics and clinical outcome of in-vitro maturation (IVM) treatment cycles with and without in-vivo matured oocytes collected following human chorionic gonadotrophin (HCG) priming. The patients were administered 10,000 IU of HCG subcutaneously when endometrial thickness reached > or =6 mm and oocyte collection was performed 35-36 h after HCG administration. The clinical outcome and embryological aspects were analysed between IVM cycles with (group 1) and without (group 2) in-vivo matured oocytes. In group 1, three (range 1-12) in-vivo matured oocytes per patient were retrieved on average. The number of good quality embryos derived from in-vivo matured oocytes in group 1 was significantly higher than those derived from in-vitro matured oocytes in group 1 and group 2 (P < 0.05). However, there was no difference between the number of good quality embryos produced from in-vitro matured oocytes in the two groups. There were 12 clinical pregnancies (40.0%) in group 1, and seven pregnancies (23.3%) in group 2. These results suggest that IVM cycles with in-vivo matured oocytes resulted in a good clinical pregnancy rate, which could be explained by the superior quality of embryos derived from the in-vivo matured oocytes.

Selection of the optimal day for oocyte retrieval based on the diameter of the dominant follicle in hCG-primed in vitro maturation cycles

BACKGROUND The efficiency of in vitro maturation (IVM) techniques is suboptimal compared with controlled ovarian stimulation combined with IVF cycles, and studies are needed to identify factors that predispose IVM cycles to success or failure. We compared the outcome of IVM cycles with different dominant follicle (DF) size at oocyte retrieval following hCG priming. METHODS IVM was performed in 160 patients with polycystic ovaries (171 cycles). We administered 10,000 IU hCG s.c. 35-38 h before oocyte collection when endometrial thickness reached at least 6 mm. IVM cycles were retrospectively analyzed according to DF diameter as follows; Group 1: DF diameter <or=10 mm, Group 2: between 10 and 14 mm, Group 3: >14 mm. RESULTS A positive correlation was observed between DF size and number of in vivo matured oocytes collected (Group 1, 2 and 3 = 6.9, 10.6 and 15.1%, respectively). The rates of IVM, fertilization and embryo development were similar among the sibling immature oocytes collected from the three groups. However, clinical pregnancy rate in Group 2 (40.3%) was higher than Group 3 (17.1%) (P < 0.05). Moreover, implantation rates in Groups 1 (13.6%) and 2 (14.3%) were higher than Group 3 (4.9%) (P < 0.01). CONCLUSIONS Our results suggest that oocyte collection in IVM cycles should be performed when the DF is 14 mm diameter or less. Sibling immature oocytes may be affected detrimentally if a DF >14 mm is present at oocyte collection.

Fertility preservation treatment for young women with autoimmune diseases facing treatment with gonadotoxic agents

OBJECTIVE To describe a case series of seven women with SLE and other systemic autoimmune rheumatic diseases (SARDs) who required cyclophosphamide therapy and underwent fertility preservation treatments. METHODS Of the seven patients reported here, five women had SLE with nephritis, the sixth had immune thrombocytopenia purpura (ITP) and the seventh had microscopic polyangiitis (MPA) with renal involvement. All women were nulliparous and younger than 35 yrs. RESULTS Patients with SLE underwent in vitro maturation (IVM) of immature oocytes aspirated during a natural menstrual cycle followed by vitrification of the matured oocytes if a male partner was not available, or vitrification of embryos if one was available. The patient with ITP and the patient with MPA underwent gonadotropin ovarian stimulation followed by oocyte or embryo vitrification. All women completed fertility preservation treatment successfully and mature oocytes or embryos (36 and 13, respectively) were vitrified. No complications were associated with this treatment and cytotoxic therapy was initiated as scheduled in all cases. CONCLUSIONS Oocyte or embryo cryopreservation should be considered for fertility preservation in young women with SARDs who face imminent gonadotoxic treatment. In patients, where gonadotropin ovarian stimulation is deemed unsafe, IVM of immature oocytes, aspirated during a natural menstrual cycle, followed by vitrification or fertilization of the mature oocytes, seems to be safe and feasible. For patients in whom hormonal ovarian stimulation is not contraindicated, this method may be considered depending on the urgency to start cytotoxic therapy.

Elevated serum β-human chorionic gonadotropin in nonpregnant conditions

Positive serum β-human chorionic gonadotropin (β-hCG) in reproductive-age women generally indicates a pregnancy, and to a lesser extent, gestational trophoblastic disease, ovarian or peripheral germ cell tumor. Besides gynecologic conditions, nongynecologic cancers can be associated with β-hCG positivity as well. The hormone in these tumors varies from detection by the immunohistochemistry studies of the tumor tissue only to a high serum level. This is illustrated by our case report of a 26-year-old woman who was diagnosed with a spindle cell osteosarcoma of the shoulder. The serum β-hCG became undetectable after chemotherapy. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall that elevated serum hCG can be related to pregnancy, gestational neoplasias, and ovarian and nongynecologic tumors and explain that it is important to appreciate that the hCG detected in these conditions may differ in type and be a marker of the success of treatment.

Comparison of low-dose human menopausal gonadotropin and micronized 17β-estradiol supplementation in in vitro maturation cycles with thin endometrial lining

OBJECTIVE A challenge of in vitro maturation (IVM) treatment in some women is insufficient development of the endometrium prior to embryo transfer. DESIGN Retrospective study. SETTING McGill Reproductive Center, Montreal, Canada. PATIENT(S) Women with endometrial thickness <6 mm on days 6-10 ultrasound (US) scan of IVM treatment. INTERVENTION(S) In the human menopausal gonadotropin (hMG) group, 150 IU/day of hMG was started and in the estradiol group, 6 to 12 mg/day of micronized 17beta-estradiol was initiated. Additional US scans were performed 2 to 3 days apart, until endometrial thickness reached > or =8 mm or a dominant follicle (>10 mm) was identified. MAIN OUTCOME MEASURE(S) Endometrial lining before oocyte retrival. RESULT(S) In both groups endometrial lining significantly thickened following treatment. However, hMG treatment resulted in a higher number of follicles > or =7 mm compared to estradiol (7.4 +/- 4.8 vs. 3.4 +/- 2.5, respectively) and a significantly higher percentage of mature oocytes that were identified on the day of oocyte retrieval (in vivo matured oocytes) (15.1% vs. 10.5%). CONCLUSION(S) In IVM designated cycles with a thin endometrium both low-dose hMG and micronized 17beta-estradiol supplementation significantly improve endometrial thickness. However, low-dose hMG results in larger follicles and a greater number of in vivo matured oocytes.

A unique biological in-vivo model to evaluate follicular development during in-vitro maturation treatment

The aim of this study was to identify the size in which the dominant follicle acquires the ability to produce a functional corpus luteum. This observational study includes 15 women with ovulatory cycles who underwent human chorionic gonadotrophin (HCG)-primed in-vitro maturation (IVM) treatments without embryo transfer. All patients received subcutaneous injection of HCG 10,000 IU 38 h prior to oocyte retrieval. Five to seven days following retrieval, serum concentrations of progesterone and oestradiol were measured along with ultrasound scan measuring the antral follicle count. Using receiver operating characteristic curves and the Youden index (J), this study clearly shows that the diameter of the dominant follicle at the time of the LH surge is a good predictor for its ability to form a progesterone-producing corpus luteum (area under the curve 0.94). These findings revealed that the dominant follicle develops the competence to form a corpus luteum, signified by the production of more than 10 nmol/l serum progesterone at 5-7 days from oocyte retrieval, as soon as it acquires a diameter of 10.5-12.0mm. In addition, a new cohort of viable antral follicles can be identified as early as 5-7 days following IVM oocyte retrieval.

Will in vitro maturation ever be used in all IVF patients

In vitro maturation of human oocytes obtained from unstimulated ovaries offers a more ‘patient friendly’ treatment option than conventional IVF treatment with ovarian stimulation to the couples undergoing assisted reproductive technologies. It has classically been offered to women who are considered high risk for ovarian hyperstimulation syndrome. Since significant progress has been made to improve the implantation and pregnancy rates using in vitro matured oocytes, the patient spectrum for in vitro maturation treatment has become wider. However, implantation and pregnancy rates of conventional IVF are still higher than those of unstimulated cycles followed by in vitro maturation. To improve the in vitro maturation outcomes, some studies have focused on improving in vitro culture conditions, whereas others have tried to improve the quality and quantity of oocytes retrieved by modifications in the follow-up of treatment cycles.

In Vitro Maturation of Oocytes Collected from Unstimulated Ovaries for Oocyte Donation

OBJECTIVE To assess the role of immature oocyte collection from unstimulated ovaries as a potential source of oocyte donation. DESIGN Prospective cohort study. SETTING A tertiary, university-based, in vitro fertilization center. PATIENT(S) Twelve oocyte donors with ultrasound-only polycystic ovaries or polycystic ovary syndrome matched with 12 oocyte recipients. INTERVENTION(S) Immature oocyte collection without any ovarian stimulation. In vitro maturation of the oocytes. Embryo transfer of the embryos. MAIN OUTCOME MEASURE(S) Immature oocyte collection, maturation, fertilization, and cleavage rates. Implantation, pregnancy, and live birth rates. RESULT(S) A mean of 12.8 +/- 5.1 Germinal-vesicle oocytes were aspirated per collection. The in vitro maturation rate was 68.3% +/- 18.4% with a mean of 8.7 +/- 3.6 mature oocytes per collection. The mean fertilization rate was 73.3% +/- 19.4%. Two to five embryos (median four) were transferred. Six recipients conceived, giving a 50% clinical pregnancy rate per cycle. The mean implantation rate per embryo was 18.2%. The live birth rate per cycle started was 30%. CONCLUSION(S) Collecting immature oocytes from unstimulated ovaries for the purpose of oocyte donation is a simple procedure that totally avoids ovarian stimulation. With appropriate selection of women with ultrasound-only polycystic ovaries or women with the polycystic ovary syndrome, the pregnancy rates of the recipients are comparable with those achieved through conventional IVF oocyte donor cycles.