In reaction to news that womb transplants may be imminent, a Hungarian newspaper expressed concern about womb peddling and the possibility of "gynecological care that routinely results in women going in for a check-up and only finding out later they've been given a hysterectomy" and "girls from the Hungarian countryside selling their wombs to rich yuppies from New York".  Akció means 'for sale (special offer)'.

Also in November 2006 Dr Giuseppe Del Priore, from New York Downtown Hospital, said he had been given the go-ahead to carry out a womb transplant operation and claimed to have found a number of potential donors.  Dr Del Priore said: "It is cautionary approval but it is approval. If the right patient shows up the [hospital] independent review board has stated we could go-ahead. Technically we are capable of doing it. If we had everything in order we could do it tomorrow."  However any would-be patient will have to go through months of counselling and tests before approval - including seeing a psychologist and reconsidering adoption or surrogacy, as well as seeing a pregnancy risk specialist and transplant support team. The organ is likely to be sourced from a dead donor who had previously had a child. They would have to have the same blood group and be immunologically matched.

The long race for the first successful uterus transplant and pregnancy reached another small milestone when in October 2009 Dr Richard Smith- a consultant gynaecological surgeon at Hammersmith Hospital in London - claimed that his teams research on animals had “cracked” how to ensure a good blood supply to a transplanted womb. 

The Hammersmith team now hope to be able to give women a new womb for long enough to allow them to conceive and give birth.  They could use eggs from a donor fertilised by their partner and placed in the implanted uterus.  After birth, they would then remove the organ, to reduce the women’s exposure to the high strength immune suppressing drugs most transplant patients have to take all their lives. 

Procedure for the removal of a Uterus from a Living Donor Step  1. The uterus is taken from the donor through an incision in the abdomen and placed on a bed of ice Step 2. The blood vessels to the uterus is flushed with cold preservation solution Step 3. The three hour operation of the donor ends after the top of the vagina is sewn up.

However Hammersmith and Gothenburg may have been overtaken in the race by doctors at Akdeniz University Hospital in southern Turkey.  On  9th August 2011 they transplanted -in a seven hour operation - a uterus from a woman who had died in a car crash to a genetically XX 21 year old woman, Derya Sert, who was born without a uterus.  Micro-surgeon Omer Ozkan, said: "The surgery was a success ... [But] we will be successful when she has her baby. ... For now we are happy that the tissue is living.'

Mrs Derya Sert

Mrs Sert then spent six months in hospital and was given powerful immunosuppressant drugs to stop her body rejecting the new womb. However her periods started just three weeks after the operation, a signal that the new womb was working well.  Scans showed its lining to be healthy - Doctor Munire Erman Akar said "We can see it from the ultrasound that the endometrium lining is perfect", but added that if she did became pregnant "there are many risks like congenital anomalies because of the immunosuppressive (drugs), and intrauterine growth retardation, preterm labour."  Lowering the dose of the drugs is critical for Mrs Sert to carry a healthy baby through pregnancy.

The next step will be an IVF procedure planned for September 2012, when up to two of the eight embryos created from Mrs Sert’s eggs and her husband’s sperm, and frozen ahead of the transplant, will be inserted into her womb.

Both donating women started in-vitro fertilisation before the surgery, and frozen embryos could be thawed and transferred to transplanted uterus' if the receiving women are considered in good enough health after a year-long observation period.  "We are not going to call it a complete success until this results in children," said Michael Olausson, one of the Swedish surgeons.

 

Ectopic Pregnancy

Ectopic pregnancy - the development of the baby outside the uterus (womb) - is another promising approach for transsexual women seeking to become pregnant.  Natural occurrences of ectopic pregnancy do a occur, however they are considered very dangerous to the mother and subsequent live births are very rare (one pregnancy in millions).  However it is possible that the first babies with transsexual mothers will be born this way because of the initial simplicity - no difficult transplants of a uterus or other organs.

The technique would involve attaching the foetus (the term used for developing babies under 8 weeks from conception) to the muscles inside the transsexual woman's abdomen, or even fashioning a [disposable] artificial womb from abdominal tissue.  Attachment to the bowel, with its good blood supply, is another attractive option, but perhaps the worst in terms of post delivery trauma.  

Preliminary female hormone treatment will be vital for supporting and encouraging the foetus' placenta to produce enzymes which then eat into whatever internal organ it is placed on, so that the placenta can attach and tap into the blood vessel to obtain nutrition.  The baby will then develop inside the woman's abdomen, and the woman will carry the baby for its full term before giving birth by caesarean section. 

Sustaining the pregnancy will require further large amounts of female hormones to be taken, in particular high levels of oestrogen and progesterone must be maintained during the first three month of pregnancy.  The feminising effects of these may be a problem for a man who wants to become pregnant but doesn’t wish to develop breasts, but it's hardly a problem for a MTF transsexual woman who takes such hormones every day of her life!

There are though two main catches to this procedure:

• Firstly, there is a severe risk of a massive haemorrhage (copious bleeding from damaged blood vessels) when the ectopic ruptures; this is actually the most common cause of women dying in pregnancy.
• Secondly, if the foetus is implanted in a place where it can thrive without killing the mother, then it can grow to the point where it is a viable baby and can be delivered surgically.  However, this leaves the big problem of what to do about the implantation site.  While the uterus is designed to cope with the eight-inch wound left when the placenta separates; other organs have no mechanism for helping the placenta to separate and then contracting around themselves to stop the bleeding.  Current medical practice with genetic women is to cut the umbilical cord close to the placenta and leave it inside the uterus.  If all goes well, it will eventually shrink and be reabsorbed, however with transsexual women there would be a serious risk of infection and other complications with this approach, and surgical removal may be the marginally better option. 

There is a real possibility that the mother will require urgent life saving surgery, either during her pregnancy, immediately after the caesarean, or during the recovery period afterwards.

Procedure
Assuming the mother and her medical team have determined that the risks are acceptable, the exact process for an ectopic pregnancy is:

Step 1: Hormones
Suitable doses of female hormones are administered to make the transsexual woman receptive to the pregnancy.

Hormone levels in a woman during pregnancy, after steadily building up for 9 months,
progesterone and oestrogen levels drop precipitously after the birth.

Step 2: Implantation IVF (in vitro fertilisation) techniques are used to obtain and fertilise egg(s), and then induce an ectopic pregnancy by implanting an embryo and its placenta into the abdominal cavity, into or just under the peritoneum.  The peritoneum is the smooth serous membrane which lines the cavity of the abdomen, it surrounds the large interior organs and forms a nearly closed sac. Step 3: Embryo Growth Once implantation is complete and the embryo is established, hormone treatment can be reduced because the pregnancy itself will take over.  The embryo secretes sufficient hormones to maintain its own growth and development. Step 4: Growth of the Foetus The foetus will be carefully monitored during its development, i.e. foetal heart monitoring, chronic villus sampling, ultrasound scanning, and a constant watch kept over the mother's health. Step 5: Delivery The delivery will requires open surgery (Caesarean section) to remove the baby and the placenta. Removal of the placenta is the real danger because it forms such intimate connections with surrounding vessels that a massive haemorrhage is likely.   Implantation may have also involved other structures in the abdomen, including the bowel and it is possible that parts of other organs may need to be removed.

Website
On first appearances the website "Pop! The First Male Pregnancy" seems to be monitoring the first ever male pregnancy by the Ectopic method.  But it would also have to be the longest pregnancy ever, the site having first being brought to my attention in 2000!  There is however an obscurely located disclaimer: "This site was created to be an exploration of a very likely scenario that may one day result from new advances in biotechnology and infertility treatments. .... the information contained on the Site is not represented as being factually accurate."   Although a sophisticated hoax, the web site is still worth a brief browse.

Genetic Parentage

Up until our current time, embryos have always been formed by the union of a sperm (supplied by a XY male) and an egg or ovum (supplied by a XX female).  Both the sperm and the ovum provide DNA, but the ovum also provides a “house” in which the embryo grows during the early stages of development.  An ovum is therefore absolutely essential for reproduction.

A post-SRS transsexual woman faces two major problems in passing her genes on to a child, regardless of whether this is to be carried by a surrogate mother or [in the future] by the transsexual woman herself.  Firstly she lacks her own ovaries to produce ovum containing her genes, and secondly having a baby with her husband or a male partner would involve the genetic union of two males - known as "same-sex parenting".

One method for providing the embryo to be implanted is to obtain an egg from an unrelated woman and have it fertilised by sperm from the husband or partner.  But while this method is already occasionally used (the baby being carried to term by a surrogate mother), this approach is unsatisfactory for transsexual woman as she has no genetic relationship with her baby.

However, there are several other options that a transsexual woman can take in order to be genetically related to her baby:

1. If possible, before sex re-assignment surgery, she could have a sperm sample frozen, indeed nearly half of MTF transsexual patients now make this provision before their SRS.  The unfrozen sperm could then be used to fertilise a donated ovum (egg) from an unrelated woman.  The mother would then have normal 50% shared genes with the baby, but unfortunately the husband/partner would have no genetic relationship unless the ovum came from a close female relative such as a sister.
   
2. If no sperm sample is available, then the transsexual's sister or even her mother could donate an ovum for fertilisation by the father - in this instance the transsexual mother will share 25% of her babies genes, and her husband/partner a normal 50%.

In the next few years there may become available several new and exciting options which use a cloning technique called "membrane fusion" to create a fertilisable egg:

3. An unrelated woman donates an ovum.  The nucleus, containing this woman's DNA, is removed, and an "X" bearing nucleus from one of the transsexual woman's sperm (again frozen from a sample taken before SRS) is put in to its place, creating an unfertilised egg.  The new ovum can then be fertilised by the father's sperm and both the mother and her husband/partner will have a normal 50% share of the baby's gene's.

   Several research teams have reported successes in creating such reconstituted or "hybrid" human eggs, although none have [publicly at least] so far been fertilised for legal reasons - indeed there is a real possibility some countries will make this type of research illegal. 

4. An unrelated woman donates an ovum.  The nucleus, containing this woman's DNA, is removed, and a nucleus with two sets of chromosome from one of the transsexual woman's cells is put in to its place.  Half the genetic material is removed, creating an unfertilised egg with just one set of chromosomes.  The new ovum can then be fertilised by the father's sperm and both the mother and her husband/partner will have a normal 50% share of the baby's gene's.

1. Nucleus from a cell of the transsexual woman is removed and transplanted into a donor egg cell from another woman. 2. The hybrid egg cell which now contains the genes of the transsexual woman is fertilised. 3. Transsexual mother is implanted with the embryo, becomes pregnant and eventually gives birth.

And finally, the most advanced and technically challenging option of all:

5. Human embryonic stem cells are developed in the laboratory into primordial germ cells, a form of cell that can subsequently become follicle eggs (or sperm).  This approach potentially allows an engineered egg to produced from a transsexual woman.  Research with mice has confirmed that the first steps are possible, although many obstacles remain.

Approach 4 is perhaps the most promising in the short- to medium-term.  On 5 Sept 1999 the UK's Sunday Times reported a major advance by a team headed by Zev Rosenwaks at the Cornell University Medical Center, New York.  They had been able to take immature egg cells from the ovaries of a donor, remove the nucleus (containing the donor's genetic material) and replace it with genetic material taken from an ordinary body cell of another animal.  The researchers have found they can reprogramme the DNA genetic blueprint from any living cell to make it behave like an unfertilised egg.  The donor egg cell thus acts as an "envelope" for the prospective genetic mother's genetic material.  Once the reconstituted egg cell is mature, it could be fertilised in the laboratory using IVF techniques and the embryo then implanted in to the womb or abdomen of the mother.  Rosenwaks said: "We are primarily working with animals, but the work is also being pursued in humans. We have no human pregnancies yet.". 

In June 2001 the fertility researchers from Cornell University reported that they had now created viable manufactured human eggs using human eggs donated by women undergoing in-vitro fertilization.   The experimental procedure uses genetic material from a cell taken from the infertile woman and transplants that material into a donor egg, which has had its genetic material removed.  

The process is somewhat similar to the cloning technique that was used to create Dolly, the first cloned sheep.  There is, however, a crucial difference: Cornell is using only half of the genetic code contained in the adult cell - that of the mother.  All adult cells carry two sets of chromosomes, one from the mother and a second from the father, so half have to be removed before fertilisation can occur.  To do this, the researchers harness the natural ability of the egg to make this happen, using a tiny electrical current, or chemicals, to activate the process of splitting the normal cell's nucleus in half.  One half is then taken away so that the reconstructed egg will - according to Professor Palermo, who an assistant professor at the Center for Reproductive Medicine and Infertility at Cornell University Medical Center - "closely resemble a natural, mature human egg", which has only one set of chromosomes.  However success rate is low, out of 200 attempts, 17 of the eggs were "haploidised" or made to have the correct number of chromosomes.

The second set of chromosomes will come from the fathers sperm, which also only carries a single chromosome set.  To fertilise the eggs, sperm would have to be injected through the cell wall just before the electric shock.  The Cornell team has not tried human eggs, but has tried fertilising artificial mice eggs with some success.  

Clearly great progress is being made with this technique which offers considerable hope to transsexual women, but there are still some major potential problems.  If sperm is not available then there is concern that using "old" DNA from cells in the mother's body could mean that the new-born baby was the genetic age of the mother.  Studies of Dolly the sheep, the first animal to be wholly cloned, suggested that her cells were much older than her chronological age - she prematurely suffered from many medical problems normally associated with old age, and finally had to be put down in 2003 while still relatively "young".  Also, some genes are chemically labelled as coming from the mother or the father - a process called "imprinting".  These labels would have to be changed, otherwise the resulting embryo would be defective.  Finally there are problems with the sex chromosomes, it is possible to produce embryos with an abnormal set of sex chromosomes and it would for example be necessary to screen the individual sperms to make sure the right combination of sex chromosomes was used.  But this would have the bonus of letting the couple choose whether to have a son or a daughter.

Dr Ursula Eichenlaub-Ritter, who is a professor of gene technology at the University of Beilefeld in Germany, says that Palermo's technique has the same problems as cloning: It requires many, many failed experiments before a viable egg is produced.  She says that she doesn't think the technology is an efficient way to produce this kind of egg.... "I don't see success in the near future.".  Dr Palermo thinks that clinical trials on human women are perhaps still 5 years away.

It has become clear (as of June 2002) that the increasingly common animal clones are subject to various genetic problems.   It is also expected that while humans may well be cloned imminently, the resulting progeny will be subject to similar problems.  There is also no reason to believe that the cloning related reproductive techniques just described above won't suffer such problems.   However, it is also reasonable to expect that improvements in cloning techniques and new procedures will eventually overcome these issues.

Nursing

Once the baby is born, the transsexual mother may well be able to experience the final physical act of pregnancy and birth and attempt to nurse her new baby - albeit with many assumptions such as being well enough after the delivery and her breasts are adequately developed and haven't been badly damaged by augmentation.  There are already a few instances of transsexual women lactating and even breast feeding the babies of ex-wives or female partners.

Breastfeeding normally strongly recommended by doctors, it is by far and away the best and most convenient way to feed a baby.  Not only will the baby be healthier, but it also helps the new mother lose weight more easily.  Calories are burned during milk production; indeed some of the weight gained by a woman during pregnancy is intended to be used during lactation. 

Breast augmentation, common in transsexual women, does not normally prevent breast feeding.  The main reason that breastfeeding may not be recommended or encouraged by the physician is if the drugs and other hormones being taken by the mother may make the milk unsuitable for nursing.

It's very probable that the pregnancy and birth, and the associated hormone levels, will in itself be enough to induce lactation in the mother.  

Inducing and maintaining lactation requires:

1.	During pregnancy a high level of oestrogen must be maintained in the mother.  Some will be produced by the placenta, but it will also be necessary for her to take additional doses during the pregnancy, particularly in the early stages.   After birth the oestrogen level should be suddenly dropped down, which will happen naturally with the removal or post-delivery contraction of the placenta.  In most women [transsexual or non-transsexual] this will kick the pituitary gland into releasing enough prolactin (the milk-producing hormone) to start some lactation.
2.	Along with oestrogen, progesterone plays a significant role in the development of lactating tissue (glands and ducts), so maintaining a moderate to high level of progesterone for the same period will also help.   Some progesterone will be produced by the placenta, but again it may be necessary for the mother to take additional doses during the pregnancy.
3.	Finally, assuming that lactating tissue develops and the milk comes in, it is necessary to frequently nurse in order to stimulate the milk "let-down" secretion (milk ejection) reflex - this is actually caused by the pituitary gland producing yet another hormone, oxytocin.
4.	Not a lot of milk will be produced unless suckling is frequent and consistent, about every 2-3 hours.  Less stimulation than that, say once every 5-8 hours, will result in dramatically less milk production.  Even less than that will result in complete cessation of milk production some 1-3 weeks after it starts.   If nursing is not immediately and regularly possible then in order to maintain milk flow (assuming that this is required), it will be necessary to artificially stimulate let-down, for example by: relaxing with the baby, hearing or thinking of the baby being hungry, direct sucking stimulation of the nipples and immediately surrounding tissue, orgasm, etc.