Professor Gerald SchattenPittsburgh Development Center

Professor, Vice-Chair and Division Director of Ob-Gyn-Repro Sci, and Professor of Cell Biology, Cancer Institute, & of Bioengineering

University of Pittsburgh Schools of Medicine & EngineeringGSchatten@pdc.magee.edu

SARG in 2058 CE:  

Anticipating the Next Forty Years of IVF Innovations

SHORT REPORT Open Access

Case Report: Induced Lactation in a Transgender WomanTamar Reisman1,2,* and Zil Goldstein1

AbstractObjective: Our report describes a case of nonpuerperal induced lactation in a transgender woman.Methods: Wepresent the relevant clinical and laboratory findings, along with a review of the relevant literature. Results: A 30‐year‐old transgender woman who had been receiving feminizing hormone therapy for the past 6 years presented to our clinic with the goal of being able to breastfeed her adopted infant. After implementinga regimen of domperidone, estradiol, progesterone, and breast pumping, shewas able to achieve sufficientbreast milk volume to be the sole source of nourishment for her child for 6weeks. This case illustrates that, in some circumstances,modest but functional lactation can be induced in transgenderwomen.

Keywords: breastfeeding; gender dysphoria; induced lactation; transgender

History of Present IllnessA 30-year-old transgender woman presented to clinic seeking help to achieve her goal of breastfeeding. She

explained that her partner was pregnant but not inter-ested in breastfeeding, and that she hoped to take on

the role of being the primary food source for her infant. The patient’s medical historywas significant for gender

incongruence for which she initiated a feminizing hor-mone regimen in 2011. At the time of our first visit, she was taking spironolactone 50 mg po bid, estradiol2mg

po bid, and micronized progesterone 100 mg po bid. Her medical history was also significant for panic disor-

der, for which she was taking occasional clonazepam, and insomnia, for which she was taking occasional zolpi-

dem. She was otherwise known to be in good general health and reported no complaints. Apart from her use

of oral estradiol, she had no known risk factors for throm-boembolism. She did not have a personal or familial his-

tory of thromboembolism and was a nonsmoker.Her surgical history was notable only for laparo-

scopic cholecystectomy. She had not had any gender-affirming surgeries such as breast augmentation, orchi-ectomy, or vaginoplasty.

On initial examination the patient was a pleasant, wellnourished, well developed woman who appeared her sta-ted age. Her breasts were noted to be Tanner stage V.

Her laboratory results from her initial evaluationincluded estradiol 119 pg/mL, progesterone 8.70 ng/mL, prolactin 9.5 ng/nL, sex hormone binding globulin48 nmol/L, and total testosterone 256 ng/dL.

CoursePrevious investigators have reported the followingbasic framework for nonpuerperal induced lactation:(1) increased estradiol and progesterone dosing tomimic high levels seen during pregnancy, (2) use of agalactogogue to increase prolactin levels, (3) use of abreast pump with the speculation that it would increaseprolactin and oxytocin levels, and (4) subsequent re-duction in estradiol and progesterone levels, with theintention of mimicking delivery.1–6

The patient obtained domperidone from Canada, anantiemetic used off-label as a galactogogue internation-ally.7 The patient was started on domperidone 10 mgpo tid. The patient also was given instructions to useher breast pump for 5 min per breast TID.

Transgender Health Volume 3.1, 2018DOI: 10.1089/trgh.2017.0044

Transgender  Health

1Center for Transgender Medicine and Surgery, New York, NewYork.2Department of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, New York.

*Address correspondence to: Tamar Reisman, MD, Center for Transgender Medicine and Surgery, 275 7th Avenue, 12th Floor, New York, NY 10011, E-mail: tamar.reisman@mssm.edu

ª   Tamar Reisman and Zil Goldstein 2018; Published by Mary Ann Liebert, Inc. This is an Open Access article distributed under the terms of the Creative  Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

24

Blastocyst‐like structures generated solely from stem cells•Javier Frias-Aldeguer, .......&Niels Geijsen

•Nature 557, 106–111 (2018)

H.R.2029  ConsolidatedAppropriations Act114th Congress 

• (Sec. 749) Prohibits the FDA from acknowledging applications for an exemption for investigational use of a drug or biological product in research in which a human embryo is intentionally created or modified to include a heritable genetic modification. Provides that any submission is deemed not to have been received, and the exemption may not go into effect.

BIOETHICS FORUM ESSAY

Do We Have a Moral Obligation to GeneticallyEnhance  our Children?

https://www.thehastingscenter.org/moral-obligation-genetically-enhance-children/

By Ronald M. Green

The Oxford philosopher Julian Savulescu, among others, has argued that prospective parents engaging in embryo selection using preimplantation genetic

diagnosis not only may seek to havegenetically enhanced children but are morally obligated do so. (See, for example, his essay “Procreative Beneficence:Why WeShould Select the Best Children,”Bioethics, 15, no.5/6, 2001.)

Iargue that Savulescu is wrong.

Savulescudefends amoral principle he calls the principle of procreative beneficence. He states that, under this principle, prospective parents choosing amongembryos “should select the child, of the possible children they could have,who is expected to have the best life, or at least as good a life as the others, based on the relevant, available information.” Among the possible enhancements he identifies are intelligence, memory, self-discipline, impulse control, foresight,

patience, and a sense of humor. Savulescu has not yet extended this principle beyond preimplantation genetic diagnosis to gene editing. He acknowledges thatgene editing currently carries health risks not associated with embryo selection, and that these risks outweigh any obligation to try to bring about “the best life”for achild.

But given the speed with which CRISPR technology is advancing, it seems that we are not far away from safe, effective gene enhancements for some traits. So

according to Savulescu’s principle, when sufficient levels of safety are reached, all parents with the means to afford gene editing for enhancement will have a moralobligation to do so.

Iwill specify my criticisms of Savulescu’s principle, but first Iwant to say that Ifully support the reproductive use of geneediting technology for the prevention and

elimination of serious genetic diseases. If we could use gene editing to remove the gene sequences in an embryo that cause sickle cell diseaseor cystic fibrosis, Iwouldsaynot only that we may do so, but in the case of such severe diseases, that we haveamoral obligation to do so.

I think that parents and medical professionals should always try to give a child a healthy start in life. This principle underlies the very firm moral intuition thatpregnant women should not take drugs or drink alcohol to excess during pregnancy. Inan era of safe geneediting, Ibelieve it would extend to the obligation to use

this technology to avoid transmitting grave inherited disease conditions.

In 1873, Harvard Professor Edward H. Clarke wrote a well received book in which he claimed to have found the reason for

“female sterility,” as infertility was then called.

The culprit, he said, was the education of women, which diverted energy from the reproductive machinery to the brain,

resulting in women with “monstrous brains and puny bodies.”

ArticleLive birth derived from oocyte spindle transfer to prevent mitochondrial disease

John Zhang a,b,*, Hui Liu b, Shiyu Luo c, Zhuo Lu b, Alejandro Chávez-Badiola a, Zitao Liu b, Mingxue Yang b, Zaher Merhi d, Sherman J Silber e, Santiago Munné f, MichalisKonstandinidis f, Dagan Wells f, Jian J Tan g, Taosheng Huang c,*a New Hope Fertility Center, Punto Sao Paulo, Lobby Corporativo, Américas 1545 Providencia, Guadalajara, Mexicob New Hope Fertility Center, 4 Columbus Circle, New York, NY 10019, USAc Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, OH 45229, USAd Department of Obstetrics and Gynecology, Division of Reproductive Biology, NYU School of Medicine, 180 Varick Street, New York, NY 10014, USAe Infertility Center of St Louis, St Luke’s Hospital, St Louis, MO 63017, USAf Reprogenetics, 3 Regent Street, Livingston, NJ 07078, USAg Department of Obstetrics and Gynecology, The Mount Sinai Hospital, E 101st Street, New York, NY 10029, USA

Dr John Zhang completed his medical degree at Zhejiang University School of Medicine in China, and subse-quently received his Master’s Degree at Birmingham University in the UK. In 1991, Dr Zhang earned his PhD inIVF, and, after researching the biology of mammalian reproduction and human embryology for nearly 10 yearshe completed his fellowship training in Reproductive Endocrinology and Infertility at New York University’s Schoolof Medicine in 2001. Dr. Zhang continues his clinical research in minimal stimulation IVF, non-embryonic stemcell, long-term oocyte cryopreservation, and oocyte reconstruction by nuclear transfer.

KEY MESSAGEWe report a live birth after oocyte spindle transfer to prevent transmission of the mitochondrial disease, Leigh syndrome.

A B S T R A C T

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is oftenassociated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited.Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, isa novel technology for preventing mtDNA transmission from oocytes topre-implantation embryos. Here, we report a female carrier of Leigh syndrome (mtDNA mutation 8993T > G), with a long history of multiple undiagnosed pregnancy losses anddeaths of offspring as a result of this disease, who underwent IVF after reconstitution of her oocytes by spindle transfer into the cytoplasm of enucleated donor oocytes. A maleeuploid blastocyst was

Douglas C. Wallace

Mitochondrial DNA Variation in Human Radiation and DiseaseCell, Volume 163, Issue 1, 2015, 33–38

http://dx.doi.org/10.1016/j.cell.2015.08.067

From:  Anderhub, SJ, Kramer, A, and Maier, B.  Cancer Letters 322(2012) 8‐17

CentrosomeStructure

Gerald SchattenOregon Regional Primate Research Center and 

Oregon Health Sciences UniversityPortland OR, USA 

Human Reproduction, Vol.31, No.12 pp. 2811–2820, 2016

Advanced Access publication on October 5, 2016 doi:10.1093/humrep/dew245

O R I G I N A L A R T I C LE Reproductive epidemiology

Semen quality of young adult ICSI offspring: the first results

F. Belve, M. Bonduelle, M. Roelants, D. MichielsenA. Van Steirteghem, G. Verheyen, and H. Tournaye

MAIN RESULTS AND THE ROLE OF CHANCE: Young ICSI adults had a lower median sperm concentration(17.7 million/ml), lower median total sperm count (31.9 million) and lower median total motile sperm count(12.7 million) in comparison to spontaneously conceived peers (37.0 million/ml; 86.8 million; 38.6 million,respectively). The median percentage progressive and total motility, median percentage normal morphologyand median semen volume were not significantly different between these groups. After adjustment forconfounders (age, BMI, genital malformations, time from ejaculation to analysis, abstinence period), thestatistically significant differences between ICSI men and spontaneously conceived peers remained: analmost doubled sperm concentration in spontaneously conceived peers in comparison to ICSI men(ratio 1.9, 95% CI 1.1–3.2) and a two-fold lower total sperm count (ratio 2.3, 95% CI 1.3–4.1) and totalmotile count (ratio 2.1, 95% CI 1.2–3.6) in ICSI men compared to controls were found. Furthermore,compared to men born after spontaneous conception, ICSI men were nearly three times more likely tohave sperm concentrations below the WHO reference value of 15 million/ml (adjusted odds ratio(AOR) 2.7; 95% CI 1.1–6.7) and four times more likely to have total sperm counts below 39 million(AOR 4.3; 95% CI 1.7–11.3). In this small group of 54 father–son pairs, a weak negative correlationbetween total sperm count in fathers and their sons was found.

Intrinsically Disordered Proteome of Human Membrane‐Less Organelles

Intrinsically Disordered Proteome of Human Membrane‐Less Organelles

al‐kimiaالكيمياء

PluripotentStem Cell

Functional Haploid Cell

SpermatogonialStem Cell

Transplantation into the testis Fertilization by ICSI

In vitroSpermatogenesis

Figure 1

Source: Cell Stem Cell , Volume 11, Issue 5, Pages 715‐726 (DOI:10.1016/j.stem.2012.07.017)

Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 3

Source: Cell Stem Cell , Volume 11, Issue 5, Pages 715‐726 (DOI:10.1016/j.stem.2012.07.017)

Copyright © 2012 Elsevier Inc. Terms and Conditions

TESTICULAR

Spermatogonial stem cell transplantation into Rhesus testes regenerates spermatogenesis producing functional sperm.

Hermann, B…Schatten, G, Mitalipov, S, Orwig, K. Cell Stem Cell (2012)

Spermatogonial stem cell transplantation into Rhesus testes regenerates spermatogenesis producing functional sperm.

Hermann, B…Schatten, G, Mitalipov, S, Orwig, K. Cell Stem Cell (2012)

1. Save SSCs2. Render Infertile3. Recover4. Transplant Viable SSCs5. Spermatogenesis6. Natural or A.I.

Spermatogonial stem cell transplantation into Rhesus testes regenerates spermatogenesis producing functional sperm.

Hermann, B…Schatten, G, Mitalipov, S, Orwig, K. Cell Stem Cell (2012)

1. Save SON’s SSCs2. SON Recovers3. Render DAD Infertile4. DAD Recovers5. Transplant SON’s SSCs TO DAD6. SON’s Spermatogenesis IN DAD7. Natural  Cryo, then A.I. After 

Vasectomy