co-transplantation-human-ovarian-tissue-with-engineered-endothelial

Co-transplantation of Human Ovarian Tissue with Engineered Endothelial Cells: A Cell-based Strategy Combining Accelerated Perfusion with Direct Paracrine Delivery

Infertility is a frequent side effect of chemotherapy and/or radiotherapy and for some patients, cryopreservation of oocytes or embryos is not an option. ...

Weill Cornell Medical College

Many women affected with breast cancer are in their reproductive prime and at the time of their initial diagnosis have not yet started or completed their families. Improvements in outcomes for patients with breast cancer means longer survival times and oftentimes cures. Unfortunately, many of the treatments, while life-saving, are toxic to the finite supply of oocytes and diminish a woman's chance of future childbearing. After the initial shock of the cancer diagnosis has worn off, women are coming to the realization that their diagnosis is not a death sentence. Women that have not completed their families need to be informed about available options to protect their reproductive organs from the cancer treatments. The currently available options for fertility preservation should be discussed with every patient who is in their reproductive years prior to initiating any treatments. Fertility specialists should work closely with oncologists to counsel patients about the risks, if any, of the recommended treatment on their future fertility and discuss options to preserve potential fertility before starting treatments.

Breast cancer and fertility preservation.

Does follicular flushing during oocyte retrieval improve the number of oocytes retrieved in the poorest responders?

Follicular flushing and in vitro fertilization outcomes in the poorest responders: a randomized controlled trial.

The clinic-specific public reporting of assisted reproductive technology (ART) outcomes has been mandated by Federal law since 1992. As of late, a series of scientific and medical advances have all but deconstructed ART practice patterns thereby demanding that current reporting platforms be reevaluated for their continued ability to afford the public with credible and understandable estimates of conception per initiated cycle. In this Clinical Opinion, we trace the history of the public reporting of ART, describe the recently modified (present day) reporting platform, and explore potential future improvements thereof. 

Public reporting of assisted reproductive technology outcomes: past, present, and future.

To investigate the effect of ovarian stimulation on endometrial receptivity by comparing singleton pregnancy and perinatal outcomes following fresh or frozen-thawed blastocyst transfers.

Comparison of perinatal outcomes following fresh and frozen-thawed blastocyst transfer.

To report a case of ex vivo oocyte retrieval from oophorectomized specimens in a BRCA1 mutation carrier undergoing surgical staging for ovarian cancer.

Ex vivo retrieval and cryopreservation of oocytes from oophorectomized specimens for fertility preservation in a BRCA1 mutation carrier with ovarian cancer.

The current study investigates the utility of random-start ovarian stimulation in women desiring elective oocyte cryopreservation. Women in the study cohort underwent random-start ovarian stimulation, and were subdivided based on the phase of the menstrual cycle that ovarian stimulation began, i.e. early follicular, late follicular or luteal phase. Women undergoing conventional cycle day (CD) 2/3 ovarian stimulation start were controls. A total of 1302 women were included - 859 (66.0%) conventional CD 2/3, 342 (26.3%) early follicular, 42 (3.2%) late follicular and 59 (4.5%) luteal ovarian stimulation starts. There was no difference in the demographics or baseline ovarian stimulation characteristics. The duration of ovarian stimulation (11 versus 9 days; P < 0.001) and total dosage of gonadotrophins administered (4095.5 versus 3155 IU; P < 0.001) was higher in the random-start group. The number of total and MII oocytes in the control and random-start groups was similar. A non-significant trend towards increased cycle cancellation was noted in the late follicular start group (7.1%). Study findings indicate the number of total and MII oocytes derived from random-start protocols initiated during any phase of the menstrual cycle is similar to conventional CD 2/3 ovarian stimulation start protocols in women desiring elective oocyte cryopreservation.

Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes.

Despite major advances in tissue cryopreservation and auto-transplantation, reperfusion ischemia and hypoxia have been reported as major obstacles to successful recovery of the follicular pool within grafted ovarian tissue. We demonstrate a benefit to follicular survival and function in human ovarian tissue that is co-transplanted with exogenous endothelial cells (ExEC). ExECs were capable of forming functionally perfused vessels at the host/graft interface and increased both viability and follicular volume in ExEC-assisted grafts with resumption of antral follicle development in long-term grafts. ExECs that were engineered to constitutively express anti-mullerian hormone (AMH) induced a greater proportion of quiescent primordial follicles than control ExECs, indicating suppression of premature mobilization that has been noted in the context of ovarian tissue transplantation. These findings present a cell-based strategy that combines accelerated perfusion with direct paracrine delivery of a bioactive payload to transplanted ovarian tissue.

Engineered endothelium provides angiogenic and paracrine stimulus to grafted human ovarian tissue.

To compare the oocyte and embryo yield associated with GnRH-agonist triggers vs. hCG triggers in cancer patients undergoing controlled ovarian stimulation (COS) for fertilization preservation.

Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility preservation.

Article	Year
Breast cancer and fertility preservation. Placenta\| PubMed ID: 18790327	2008
Follicular flushing and in vitro fertilization outcomes in the poorest responders: a randomized controlled trial. Human reproduction (Oxford, England)\| PubMed ID: 24014603	2013
Public reporting of assisted reproductive technology outcomes: past, present, and future. American journal of obstetrics and gynecology\| PubMed ID: 24813599	2015
Comparison of perinatal outcomes following fresh and frozen-thawed blastocyst transfer. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics\| PubMed ID: 27388034	2016
Ex vivo retrieval and cryopreservation of oocytes from oophorectomized specimens for fertility preservation in a BRCA1 mutation carrier with ovarian cancer. Fertility and sterility\| PubMed ID: 28629583	2017
Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes. Reproductive biomedicine online\| PubMed ID: 28647355	2017
Engineered endothelium provides angiogenic and paracrine stimulus to grafted human ovarian tissue. Scientific reports\| PubMed ID: 28811567	2017
Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility pres... Fertility and sterility\| PubMed ID: 28865552	2017
Chromosomal mosaicism in human preimplantation embryos: another fact that cannot be ignored. Fertility and sterility\| PubMed ID: 29307401	2018

Glenn Schattman

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