IVF using own eggs and donor sperm

IVF can also be done by inseminating oocytes recovered on the day of the FP with donor sperm.

Legal aspects

Indications:

They are the same indications for female factor as those explained in the previous section but adding another 5:

  1. Single woman: Patient without partner wanting to get pregnant and who either has tubal factor, endometriosis, or the need for pre-implantation diagnosis or after artificial insemination failures with donor sperm.
  2. Woman with female partner: Under the same assumptions as a single woman.
  3. After several failed attempts at IVF with partner’s sperm in which we suspect male factor.
  4. In cases of azoospermia: If sperm cannot be obtained by any technique or the patient refuses it.
  5. If there is a chromosome abnormality in the man and the use of pre-implantation diagnosis is rejected.

At Eugin, there is the possibility of reserving donor sperm if available in the sperm bank, to be used, in the event of pregnancy, in a second attempt, or in a cycle in the spouse in female couples.

Methodology:

  • Visit to EUGIN to confirm the diagnosis and the treatment and to determine the type of medication regimen to be used according to the characteristics of the patient.
  • Ovarian stimulation and controls: ovarian stimulation protocols are normally used to obtain higher number of oocytes and to have a higher success rate, although a natural cycle for IVF can also be used.

The control checks in this phase are done by ultrasound in order to do a folliculometry and with a hormonal blood test every 2-3 days, the average duration of which is 8-15 days. In the event that the patient is being followed up in her country of origin by her gynecologist, the role and collaboration of the latter will be crucial in the development of the cycle.

  • Ovulation discharge: When the requirements to induce ovulation are met (usually ≥ 3 follicles of ≥ 17mm), a trigger shot for such purpose is indicated and 36h later the follicular puncture is performed. It is an outpatient procedure, usually performed under sedation, but exceptionally, local, or spinal anesthesia can also be used (only when the number of follicles is low). The night before the puncture, antibiotic prophylaxis is given orally. The patient remains under observation for about 2h after the puncture.
  • Semen sample: in this case the fertilization of the eggs will be done with a sample from a sperm donor.
  • Fertilisation: Currently there are several techniques to fertilize the oocytes, but EUGIN in> 95% of cases, uses Intracytoplasmic Sperm Injection or ICSI.
    • Conventional IVF: Each oocyte is incubated with about 50,000-100,000 sperm for several hours. It is a fertilization technique which is almost abandoned in most assisted reproduction centres.
    • IVF-ICSI: The oocytes are denuded (the somatic cell layers that surround the oocytes are removed) and a single motile sperm is microinjected into the oocyte. Initially, its indications were for severe cases of male factor but nowadays it is routinely used to increase the fertilization rate and minimize fertilisation failures.6
    • IVF-IMSI: This involves selecting a sperm through a microscope with 6000x magnifications (with conventional ICSI 400x are used). The technique is based on selecting the spermatozoa which have the most regular possible nuclei since nuclear alteration is associated with high sperm DNA fragmentation among other things. However, there is still a lack of compelling studies to demonstrate the practical effectiveness of IMSI and to determine their clear indications.
  • Embryo culture: The embryos remain in culture until the day of transfer, which is usually between 2-3 days after fertilization. In certain cases the embryos are transferred at blastocyst stage (five days after fertilization).
  • Embryo transfer: It is performed in a gynaecological box that has been specially set up for it. Under abdominal ultrasound control the embryos are gently expelled into the mid-cavity of the uterus by means of a soft, malleable catheter.7-8

In Spain a maximum transfer of 3 embryos is allowed. However, at EUGIN, this number of embryos will only be indicated in very limited cases. The number of embryos transferred will be determined primarily by the age of the woman and the existence, or otherwise, of failures in previous techniques.

If you have generated more embryos than those that have been transferred and they present a good degree of embryonic development, they will be cryopreserved for future transfer if the couple so wish.10

The complications of the puncture and ovarian stimulation, although exceptional, are hemoperitoneum post-follicular puncture, tubo-ovarian abscess, ovarian hyper-stimulation syndrome (OHSS) and ovarian torsion. In total, they constitute <1% of cases.

Success rates

Drugs:

  1. Gonadotropins

To perform ovarian stimulation in the context of an IVF cycle there are several stimulation protocols. Apart from the natural cycle, typically a controlled ovarian stimulation is carried out to obtain a suitable number of eggs that allows us to obtain a reasonable number of embryos to make an embryonic selection prior to the completion of the transfer. For this, gonadotropins are used, which can either be urinary, or recombinant.

HMG
Human menopausal gonadotropins

FSH

LH

  1. They have LH and FSH mechanism of action.
  2. Suitable for some patients(hypogonadotropic hypogonadism,…)
  1. It can be urinary (currently there are highly purified ones) or recombinant
  2. Only FSH activity
  1. Used together with FSH in certain situations

Gonadotropins are administered subcutaneously daily but, currently, long-acting subcutaneous gonadotropins are also available on the market .

2. Gonadotropin-releasing hormone analogues

GnRH analogues are applied along with gonadotropins, as it is shown that their mechanism of action controls the endogenous LH secretion thus making it possible to obtain a greater number of oocytes and of higher quality11. They can either be GnRH agonists (aGnRH) or antagonists (anGnRH).

GnRH Agonists

GnRH Antagonists

Its action, by binding to the GnRH receptor, causes an initial increase in the release of FSH and LH (flare-up effect) and subsequently its inhibition. They bind to the receptor in a competitive way so that they inhibit the secretion of FSH / LH immediately.

Ovulation triggers

Once the criterion for ovulation discharge has been reached, a drug for this action is administered.

  • The Human Chorionic Gonadotropin (ßhCG) is used in the 3 protocols which we will explain below, and may be urinary or recombinant; its LH action (as it has an almost identical molecular structure) is what allows the ovulatory action.
  • GnRH agonists can also be used but only in the cycles that followed a protocol with antagonists. The flare-up effect mentioned above is what allows the LH surge that triggers ovulation.

The main advantage of the aGnRH for ovulation is that they prevent the development of OHSS. The drawback is that this LH effect has a detrimental effect on the endometrium with a lower implantation rate, which means that the transfer cannot be made in that same cycle but that the embryos obtained have to be cryopreserved for transfer in a subsequent cycle.12

Stimulation protocols:

Types of protocols used at Eugin for an IVF cycle:

  1. GnRH Agonists:13

They can be used in:

1. Long protocol: its administration begins in the mesoluteal phase of the cycle preceding the start of the gonadoropins. It allows good control and the synchronous growth of the follicles.

2. Short protocol: they start from the 1st to 3rd day of the cycle, with the gonadotropins. It takes advantage of the flare-up effect and is used more in low responders.

 

  1. Antagonists de la GnRH:14

Its use is initiated subsequent to the administration of gonadotropins, and there are two regimens:

      1. Fixed: It is introduced from the 6th day of treatment with gonadotropins.
      2. Flexible: It is introduced with a follicle of 14mm or estradiol> 400pg/ml
  1. Natural cycle

In the natural cycle only one egg is obtained (exceptionally 2), which the woman develops physiologically in her ovulatory cycle.

Nowadays, in the clinic we use it in modified natural cycle (when we have a14mm follicle we add gonadotropins in low doses of GnRH antagonists) as it has a much lower cancellation rate than with the natural classical one.15

The natural cycle follicular puncture can be performed under local anesthesia and usually 1 single embryo is obtained, which is subsequently transferred. The endometrium also has better characteristics for implantation as it has developed physiologically, without the action of the high levels of estradiol secondary to stimulation. The main drawbacks are the lower success rates and higher cycle cancellation. Age, as in all IVF cycles, is a determining factor in the success of these techniques.

They are indicated among:

  • Patients unwilling to undergo hormone treatment or for whom it has been contraindicated for medical reasons.

Poor responders, especially when they have had previous failures of conventional ovarian stimulation.

  • Patients with previous cycles with low egg quality after stimulation.

Prevention of OHSS

One of the main drawbacks of IVF is OHSS. Today at Eugin we use several processes to prevent it:

  1. Choosing the suitable stimulation protocol according to the patient and with the appropriate dose of gonadotropin.
  2. When the patient has a risk pattern of hyper-responsiveness (antral follicle count> 14, Polycystic Ovarian Syndrome, prior OHSS, young age, ..) we always use a protocol with antagonists. When it is time for the ovulation discharge we use:
    1. ßhCG: if the response to the stimulation has been normal.
    2. aGnRH: if there is risk of OHSS, we induce ovulation with agonists and we cryopreserve the embryos for transfer in a subsequent cycle.17
  3. If an agonist protocol has been used and during stimulation a risk of OHSS was detected, a “coasting” is done, consisting of lower doses of gonadotropin, and of administering a one-off dose of antagonist rescue.18 Usually, on the next day you can indicate the ßhCG to discharge ovulation so that we reduce the risk of OHSS to the minimum.
  4. If, nevertheless, on the day of follicular puncture after using ßhCG in any protocol, > 20 oocytes are unexpectedly obtained, it may be recommended to freeze the embryos and transfer them in subsequent cycles.17

Bibliography

  1. Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978; 1: 880.
  2. Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Salpingectomy for hydrosalpinx prior to in vitro fertilization. Fetil Steril 2008; 90: S66.
  3. Ozkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and evidence-based treatments. Ann NY Acad Sci 2008; 1127:92.
  4. Silber SJ, Van Steirteghem AC, Liu J, et al. High fertilization and pregnancy rate after intracytoplasmatic sperm injection with spermatozoa obtained from testicle biopsy. Hum Reprod 1995; 10:148.
  5. Gil Raga F, Monzó A, Peinado I, et al. Análisis de los resultados de ciclos de FIV-ICSI en parejas que no gestan tras cuatro inseminaciones. Rev Iberoam Fert 2005; 22: 113.
  6. Khamsi F, Yavas Y, Roberge S, et al. Intracytoplasmatic sperm injection increased fertilization and good quality embryo formation in patients with non-male factor indications for in vitro fertilization: a prospective randomized study. Fertil Steril 2001; 75:342.
  7. Buckett WM. A review and meta-analysis of prospective trials comparing different catheters used for embryo transfer. Fertil Steril 2006; 85:728.
  8. Brown J, Buckingham K, Abou-Setta AM, Buckett W. Ultrasound versus “clinial touch” for catheter guidance during embryo transfer in women. Cochrane database Syst Rev 2010; :CD006107.
  9. Stern JE, Lieberman ES, Macaluso M, Racowsky C. Is cryopreservation of embryos a legitimate surrogate marker of embryo quality in studies of assisted reproductive technology conducted using national database? Fertil Steril 2012; 97: 890.
  10. Von Montfoort a; Fiddelers A, Janssen J, et al. In unselected patients, electice single embryo transfer prevents all multiples, but results in significant lower pregnancy rates compared with doublé embryo transfer: a randomized controlled trial. Hum Reprod 2006; 21:338.
  11. Khalaf M, Mittre H, Levallet J, et al. Gn RH agonist and Gn RH antagonist protocols in ovarian stimulation: differential regulation pathway of aromatase expression in human granulose cells. Reprod Biomed Online 201; 21:56.
  12. Youssef MA, Van der Veen F, Al.Inany HG, et al. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles. Cochrane Database Syst rev 2010; CD008046.
  13. Maheshwari A, Gibreel A, Siristatidis CS, et al. Gonadotropin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. Cochrane Database Syst Rev 2011; CD006919.
  14. Al-Inany HG, Youssef MA, Aboulghar, et al. Gonadotropin-releasing hormone antagonist for assisted reroductive technology. Cochrane Database Syst Rev 2011; CD001750.
  15. Aanesen A, Nygren KG, Nylund L, Heineman MJ. Modified natural cycle IVF and mild IVF: a 10 years Swedish experience. Reprod Biomed Online 2010; 20:156.
  16. Morgia F, Sbracia M, Schimberni M, et al. A controlled trial of natural cycle versus microdose gonadotorpin-releasing hormone analog flare cycles in por responders undergoing in vitro fertilization. Fertil Steril 2004; 81: 1542.
  17. Papanikolaou EG, Humaidan P, Polyzos N, et al. New algorithm for OHSS prevention. Reprod Biomed Online 2011; 9: 147.
  18. Hill MJ, Chason RJ, Payson MD et al.GnRH antagonist rescue in high responders at risk for OHSS results in excellent assisted reproduction outcomes. Reprod Biomed Online 2012; 25 (3):284.

Last Updated: November 2017