Emergency IVF versus ovarian tissue cryopreservation decision making in fertility preservation for female cancer patients

Capsule:
This article examines emergency IVF and ovarian tissue storage and current data on their reproductive outcomes in cancer patients. These data challenge the concept that these techniques should be labeled “experimental.”

Authors:
Karine Chung, M.D., M.S.C.E., Jacques Donnez, M.D., Elizabeth Ginsburg, M.D., Dror Meirow, M.D.

Volume 99, Issue 6, Pages 1534-1542, May 2013

Abstract:

Hundreds of thousands of women in their reproductive years are diagnosed with cancer each year. As the number of female patients who survive cancer increases, the demand for effective and individualized fertility preservation options grows. Currently there are limited clinical options for fertility preservation, and the paucity of publications describing clinical experience and outcomes data has limited accessibility to these options. Decision-making for patients diagnosed with cancer requires up-to-date knowledge of the efficacy and safety of available techniques. This article describes a step-by-step approach to evaluation of the cancer patient and presents an accumulation of clinical experience with challenges unique to patients with breast cancer and leukemia. Current data on reproductive outcomes of fertility preservation techniques are examined, demonstrating increasing evidence that these techniques are becoming efficacious enough to offer routinely to patients facing gonadotoxic cancer therapies, including those still considered “experimental.”

In vitro fertilization outcome in women with unoperated bilateral endometriomas

Capsule:
The presence of bilateral endometriomas at the time of IVF affects responsiveness to hyperstimulation but does not affect the quality of the oocytes retrieved and the chances of pregnancy.

Authors:
Laura Benaglia, M.D., Alfonso Bermejo, M.D., Edgardo Somigliana, M.D., Ph.D., Sonia Faulisi, M.D., Guido Ragni, M.D., Luigi Fedele, M.D., Juan A. Garcia-Velasco, M.D.

Volume 99, Issue 6, Pages 1714-1719, May 2013

Abstract:

Objective:
To evaluate IVF outcome in women with unoperated bilateral endometriomas.

Design:
Multicenter retrospective cohort study.

Settings:
Two infertility units.

Patients:
Thirty-nine women with bilateral endometriomas matched to 78 unexposed controls.

Interventions:
Analysis of data from patients who underwent in vitro fertilization (IVF)–intracytoplasmic sperm injection.

Main Outcome measures:
Ovarian responsiveness and oocyte quality.

Results:
Responsiveness to ovarian hyperstimulation was significantly reduced in women with bilateral endometriomas. The total number of developing follicles in cases and controls was 9.6 ± 3.3 and 14.1 ± 6.8, respectively. The number of oocytes retrieved was 7.1 ± 3.2 and 9.8 ± 5.5, respectively. Conversely, oocyte retrieval was not hampered by the presence of the ovarian endometriomas. The rate (Interquatile Range-IQR) of oocytes retrieved per total number of developing follicle in cases and controls was 77% (57-88%) and 71% (63-79%), respectively. Moreover, the quality of the retrieved oocytes did not differ. The fertilization rate (IQR) was 67% (56-100%) and 70% (57-100%), respectively. The rate (IQR) of top quality embryos per oocyte used was 33% (25-50%) and 33% (20-43%), respectively. The implantation rate was 22% and 23%, respectively. The clinical pregnancy rate and the delivery rate also did not differ.

Conclusions:
Although the presence of bilateral endometriomas at the time of IVF affects responsiveness to hyper-stimulation, the quality of the oocytes retrieved and the chances of pregnancy are not influenced.

Ovarian follicle culture advances and challenges for human and nonhuman primates

Capsule:
Recent progress in developing human and nonhuman primate follicle culture systems with the goal of obtaining competent oocytes is reviewed, and prospects for clinical application for fertility preservation are discussed.

Authors:
Evelyn E. Telfer, Ph.D., F.S.B., Mary B. Zelinski, Ph.D.

Volume 99, Issue 6, Pages 1523-1533, May 2013

Abstract:

The removal and cryo-storage of ovarian cortical biopsies is now offered as a fertility preservation option for young women. The only available option to restore fertility using this tissue is by transplantation which may not be a viable option for all patients. The full potential of this tissue to restore fertility could be achieved by the development of in vitro systems that support oocyte development from the most immature stages to maturation. The techniques of in vitro growth (IVG) combined with in vitro maturation (IVM) are being developed in human but comparing different systems has been difficult because of the scarcity of tissue and non-human primates are being used as model systems. There are many challenges to developing a complete culture system that will support human oocyte development and this review outlines the approaches being taken by several groups to support each of the stages of oocyte development using tissue from women and non-human primate models.

Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue a review of 60 cases of reimplantation

Capsule:
A review of 60 cases of frozen-thawed ovarian tissue reimplantation is presented. Cryopreservation of ovarian tissue is the only option available for prepubertal girls and for women who cannot delay the start of chemotherapy.

Authors:
Jacques Donnez, M.D., Ph.D., Marie-Madeleine Dolmans, M.D., Ph.D., Antonio Pellicer, M.D., Ph.D., Cesar Diaz-Garcia, Maria Sanchez Serrano, M.D., K.T. Schmidt, M.D., E. Ernst, M.D., Valérie Luyckx, M.D., Claus Yding Andersen, M.D.Sc.

Volume 99, Issue 6, Pages 1503-1513, May 2013

Abstract:

Aggressive chemotherapy and radiotherapy, and bone marrow transplantation (BMT), can cure >90% of girls and young women affected by disorders requiring such treatment. However, the ovaries are very sensitive to cytotoxic drugs, especially to alkylating agents. Several options are currently available to preserve fertility in cancer patients. This present review reports the results of 60 orthotopic reimplantations of cryopreserved ovarian tissue as well as the 24 live births so far reported in the literature. Restoration of ovarian activity occurred in nearly all cases. Among the 60 patients, 11 were pregnant and 6 of them already delivered 12 healthy babies. In the future, we should pay attention: 1) to improve the freezing techniques; 2) to favor the “vascular bed” before reimplantation, in order to increase the pregnancy rate. On the other hand, freezing of ovarian tissue may be combined with removal, via puncture, of small antral follicles making it possible to freeze ovarian tissue and isolate immature oocytes.

Antimüllerian hormone the assessment of the ovarian reserve and the reproductive outcome of the young patient with cancer

Capsule:
We discuss the basis for the growing use of AMH in assessment of the ovarian reserve across the lifespan, and its emerging role in assessment before and after cancer treatment.

Authors:
Richard A. Anderson, M.D., Ph.D., W. Hamish B. Wallace, F.R.C.P.

Volume 99, Issue 6, Pages 1469-1475, May 2013

Abstract:

The accurate assessment of the ovarian reserve has long been a key goal in reproductive medicine. The recognition that serum antimüllerian hormone (AMH) provides an indirect measure of the ovarian reserve has led to its rapid adoption in assisted conception, and wide exploration of its potential across the reproductive lifespan from the neonate to the menopause. In this short review we discuss its relationship with the ovarian reserve in its varied meanings, and in various contexts. These include in childhood and adolescence, and in the assessment of the impact of cancer therapy on the female reproductive tract. These therapies can adversely impact all aspects of female reproduction, including hypothalamic, pituitary and ovarian hormonal activity, and the ability of the uterus to support a successful pregnancy.

Pathogenesis consequences and control of peritoneal adhesions in gynecologic surgery a committee opinion

Capsule:
Postoperative adhesions are a natural consequence of tissue trauma and healing; however, adherence to microsurgical principles and minimally invasive surgery may help to reduce postoperative adhesions.

Authors:
The Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society of
Reproductive Surgeons

Volume 99, Issue 6, Pages 1550-1555, May 2013

Abstract:

Postoperative adhesions are a natural consequence of surgical tissue trauma and healing and may result in infertility, pain, and bowel obstruction. Adherence to microsurgical principles and minimally invasive surgery may help to decrease postoperative adhesions. Some surgical barriers have been demonstrated effective for reducing postoperative adhesions, but there is no substantial evidence that their use improves fertility, decreases pain, or reduces the incidence of postoperative bowel obstruction. This document replaces the document of the same name last published in 2008 (Fertil Steril. 2008 Nov;90(5 Suppl):S144-9).

Progesterone vaginal ring versus vaginal gel for luteal support with in vitro fertilization A randomized comparative study

Capsule:
Luteal supplementation with a weekly progesterone vaginal ring or daily vaginal gel provided similar high clinical pregnancy rates in in vitro fertilization.

Authors:
Laurel Stadtmauer, M.D., Ph.D., Kaylen M. Silverberg, M.D., Elizabeth S. Ginsburg, M.D.

Volume 99, Issue 6, Pages 1543-1549, May 2013

Abstract:

Objective:
To compare the efficacy and safety of luteal phase support in IVF with a progesterone (P) vaginal ring or gel (VR or VG).

Design:
Prospective, randomized, single-blind, multicenter, phase III clinical trial (ClinicalTrials.gov identifier: NCT00615251).

Setting:
Nineteen private and 3 academic high-volume US IVF centers.

Patients:
1,297 infertile patients were randomized to a weekly progesterone vaginal ring (VR, n=646) or a daily progesterone 8% vaginal gel (VG, n=651).

Interventions:
IVF was performed per site-specific protocols. The day after egg retrieval (ER), patients were randomized and began VR or VG therapy, which continued for up to 10 weeks’ gestation.

Main Outcome Measures:
Clinical pregnancy rates at 8 and 12 weeks of pregnancy; rates of biochemical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and cycle cancellation; and safety and tolerability were secondary measures.

Results:
Clinical pregnancy rates at 8 and 12 weeks were high and comparable between groups: 48.0% for VR and 47.2% for VG at week 8 and 46.4% (VR) and 45.2% (VG) at week 12. Live birth rates were 45% (VR) and 43% (VG). Adverse event (AE) profiles were similar between groups.

Conclusion:
The weekly progesterone VR provided similar pregnancy rates to the daily VG, with no major differences in safety.

A randomized clinical trial to evaluate the effect of granulocyte macrophage colony stimulating factor GM CSF in embryo culture medium for in vitro fertilization

Capsule:
In a prospective randomized study, addition of recombinant granulocyte-macrophage colony-stimulating factor to IVF embryo culture medium was found to increase ongoing implantation rate at gestational week 12 and live birth rate.

Authors:
Søren Ziebe, Ph.D., D.Sc., Anne Loft, M.D., Betina B. Povlsen, M.Sc., Karin Erb, M.Sc., Inge Agerholm, Ph.D., Michael Aasted, M.D., Anette Gabrielsen, M.Sc., Christina Hnida, Ph.D., Dorit P. Zobel, Ph.D., Bibi Munding, M.Sc., Susanne H. Bendz, Ph.D., Sarah A. Robertson, Ph.D.

Volume 99, Issue 6, Pages 1600-1609.e2, May 2013

Abstract:

Objective:
To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR).

Design:
Multicenter, randomized, placebo-controlled, double-blinded prospective design.

Setting:
Fourteen Scandinavian fertility clinics.

Patient(s):
A total of 1,332 women with indication for in vitro fertilization or intracytoplasmic sperm injection; 1,149 received embryo transfer (GM-CSF: n = 564; control: n = 585).

Intervention(s):
Oocytes were fertilized, and embryos cultured and transferred in control medium or test medium containing 2 ng/mL GM-CSF.

Main Outcome Measure(s):
OIR at gestational week 7, with follow-up at week 12 and birth.

Result(s):
At week 7, OIRs were 23.5% (GM-CSF), and 20.0% (control) (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.91–1.75). At week 12, OIRs were 23.0% (GM-CSF) and 18.7% (control) (OR 1.35, 95% CI 1.06–1.72), and live birth rates were 28.9% and 24.1%, respectively (OR 1.35, 95% CI 1.03–1.78). The effect of GM-CSF was influenced by the human serum albumin concentration in the medium. Birth weight and abnormality incidence were similar in both groups. Exploratory analyses showed that GM-CSF increased OIR in women with previous miscarriage, especially in women with more than one miscarriage.

Conclusion(s):
Addition of GM-CSF to embryo culture medium elicits a significant increase in survival of transferred embryos to week 12 and live birth. Our results are consistent with a protective effect of GM-CSF on culture-induced embryo stress. GM-CSF may be particularly efficacious in women with previous miscarriage.

Clinical Trial Registration Number:
NCT00565747